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For: Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J, Rozen R. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996;93:7-9. [PMID: 8616944 DOI: 10.1161/01.cir.93.1.7] [Citation(s) in RCA: 909] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

For:	Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, Selhub J, Rozen R. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996;93:7-9. [PMID: 8616944 DOI: 10.1161/01.cir.93.1.7] [Citation(s) in RCA: 909] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

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Cited by Other Article(s)

Heng TH, Walter K, Huang QQ, Karjalainen J, Daly MJ, Heyne HO, FinnGen, Malawsky DS, Kalantzis G, Genes & Health Research Team, Finer S, van Heel DA, Martin HC. Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity. Am J Hum Genet 2025;112:1316-1329. [PMID: 40306283 DOI: 10.1016/j.ajhg.2025.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 03/28/2025] [Accepted: 03/31/2025] [Indexed: 05/02/2025] Open

Abstract

Genetic association studies have focused on testing additive models in cohorts with European ancestry. Little is known about recessive effects on common diseases, specifically for non-European ancestry. Genes & Health is a cohort of British Pakistani and Bangladeshi individuals with elevated rates of consanguinity and endogamy, making it suitable to study recessive effects. We imputed variants into a genotyped dataset (n = 44,190) by using two reference panels: a set of 4,982 whole-exome sequences from within the cohort and the Trans-Omics for Precision Medicine (TOPMed-r2) panel. We performed association testing with 898 diseases from electronic health records. 185 independent loci reached genome-wide significance (p < 5 × 10-8) under the recessive model, with p values lower than under the additive model, and >40% of these were novel. 140 loci demonstrated nominally significant (p < 0.05) dominance deviation p values, confirming a recessive association pattern. Sixteen loci in three clusters were significant at a Bonferroni threshold, accounting for multiple phenotypes tested (p < 5.4 × 10-12). In FinnGen, we replicated 44% of the expected number of Bonferroni-significant loci we were powered to replicate, at least one from each cluster, including an intronic variant in patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs66812091) and non-alcoholic fatty liver disease, a previously reported additive association. We present evidence suggesting that the association is recessive instead (odds ratio [OR] = 1.3, recessive p = 2 × 10-12, additive p = 2 × 10-11, dominance deviation p = 3 × 10-2, and FinnGen recessive OR = 1.3 and p = 6 × 10-12). We identified a novel protective recessive association between a missense variant in SGLT4 (rs61746559), a sodium-glucose transporter with a possible role in the renin-angiotensin-aldosterone system, and hypertension (OR = 0.2, p = 3 × 10-8, dominance deviation p = 7 × 10-6). These results motivate interrogating recessive effects on common diseases more widely.

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Araszkiewicz AF, Jańczak K, Wójcik P, Białecki B, Kubiak S, Szczechowski M, Januszkiewicz-Lewandowska D. MTHFR Gene Polymorphisms: A Single Gene with Wide-Ranging Clinical Implications-A Review. Genes (Basel) 2025;16:441. [PMID: 40282401 PMCID: PMC12027316 DOI: 10.3390/genes16040441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2025] [Revised: 04/03/2025] [Accepted: 04/05/2025] [Indexed: 04/29/2025] Open

Abstract

The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a process essential for the methylation of homocysteine to methionine. Polymorphisms in the MTHFR gene can reduce enzyme activity, disrupting the folate cycle and leading to hyperhomocysteinemia. The two most common polymorphisms associated with this gene are 667C>T (rs1801133) and 1298A>C (rs1801131). Background: This review provides a comprehensive summary of the current knowledge regarding MTHFR polymorphisms, with a particular focus on their potential impact on disease susceptibility. We hope this review will serve as a valuable resource for understanding the significance of MTHFR polymorphisms and their complex relationships with various diseases. Methods: For this review, we prioritized recent evidence, focusing on reviews and meta-analyses published between 2015 and 2025, sourced from PubMed and Google Scholar. Results: We explore the connection between these polymorphisms and a broad spectrum of medical conditions, including cardiovascular diseases and oxidative stress pathology; neurological and psychiatric disorders, such as Autism Spectrum Disorder, Alzheimer's disease, Schizophrenia, and Major Depressive Disorder; fertility, pregnancy, and neonatal complications, including recurrent pregnancy loss, pre-eclampsia, preterm birth, low birth weight, and neural tube defects; metabolic disorders, such as diabetes mellitus, inflammatory bowel disease, and non-alcoholic fatty liver disease; and oncological conditions, including breast, prostate, and ovarian cancers; as well as leukemia, and autoimmune diseases, particularly rheumatoid arthritis. Conclusions: While some diseases have a well-established association with MTHFR polymorphisms, others require further investigation. Our analysis highlights the crucial role of environmental factors, such as ethnic background and dietary folate intake, in influencing study outcomes.

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Holborn MA, Mellet J, Joubert F, Ballot D, Pepper MS. A possible genetic predisposition to suspected hypoxic-ischaemic encephalopathy. Biochim Biophys Acta Mol Basis Dis 2025;1871:167732. [PMID: 39983557 DOI: 10.1016/j.bbadis.2025.167732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 01/27/2025] [Accepted: 02/13/2025] [Indexed: 02/23/2025]

Ramos-Rodríguez C, Rojas-Gomez A, Santos-Calderón LA, Ceruelo S, Ríos L, Ueland PM, Fernandez-Ballart JD, Salas-Huetos A, Murphy MM. The l-Arginine pathway may act as a mediator in the association between impaired one-carbon metabolism and hypertension. Biochimie 2025;230:86-94. [PMID: 39549999 DOI: 10.1016/j.biochi.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 11/13/2024] [Accepted: 11/13/2024] [Indexed: 11/18/2024]

Abstract

Elevated fasting plasma total homocysteine (tHcy) and the methylenetetrahydrofolate reductase C677T polymorphism (rs1801133) have been associated with hypertension. Whether the l-Arginine pathway is involved, is unclear. We aimed to investigate whether the association between tHcy, the rs1801133 polymorphism and hypertension involves the l-Arginine pathway. THcy, plasma folate and cobalamin, erythrocyte glutathionine reductase activation coefficient, rs1801133 genotype, plasma l-Arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in a cross-sectional study of 788 adults (aged 18 to 75), randomly selected from 2 town population registers. Participants participated in a medical checkup and provided a fasting blood sample. Associations between tHcy, rs1801133 genotype and l-Arginine pathway metabolites were assessed by multiple linear regression analysis and whether the tHcy and rs1801133 genotype are associated with hypertension via the l-Arginine pathway was investigated using mediation analysis. tHcy was positively associated with ADMA (B = 0.003; SE = 0.001; P < 0.001) and SDMA (B = 0.007; SE = 0.002; P < 0.001) and negatively associated with the l-Arginine/ADMA (B = -1.140; SE = 0.451; P < 0.05) and ADMA/SDMA (B = -0.006; SE = 0.003; P < 0.05) ratios. The MTHFR 677 CT vs CC genotype was negatively associated with ADMA (B = -0.013; SE = 0.007; P < 0.05) and with SDMA (B = -0.029; SE = 0.013; P < 0.05) in participants under 50 years. Each standard deviation increase (37.6) in the l-Arginine/ADMA ratio was associated with reduced hypertension risk (OR [95%CI], 0.6 [0.5, 0.8]). Mediation analysis showed that tHcy and ADMA were mediators in the association between the rs1801133 TT vs CC genotypes and hypertension. Our results support the l-Arginine pathway as a mediator in the association of impaired One-Carbon metabolism and hypertension.

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Li X, Zhou Z, Tao Y, He L, Zhan F, Li J. Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications. Apoptosis 2024;29:1944-1958. [PMID: 39044092 DOI: 10.1007/s10495-024-01999-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2024] [Indexed: 07/25/2024]

Yao Q, Chen X, Zhang Y, Chen H, Dou Y, He W, Sheng W, Ma X, Liu F, Yan W, Huang G. Genome-Wide Association Study Identifies Genetic Polymorphisms for Folate-Related Biomarkers in Chinese Preconception Women. J Nutr 2024;154:3592-3602. [PMID: 39374789 DOI: 10.1016/j.tjnut.2024.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 09/27/2024] [Accepted: 10/03/2024] [Indexed: 10/09/2024] Open

Abstract

BACKGROUND

Single-nucleotide polymorphism (SNP) allele frequencies, dietary habits, and folate status and their associations vary across ethnic populations. Little is known about the SNPs accounting for variations of folate-related biomarkers for Chinese preparing-for-pregnant females.

OBJECTIVES

We aimed to identify SNPs contributing to RBC and serum folate, vitamin B-12, and homocysteine concentrations in Chinese female preconception population.

METHODS

A genome-wide association study was conducted on 1000 randomly selected preconception Chinese women from the Shanghai Preconception Cohort. SNPs were genotyped using Illumina chips, and associations with biomarkers were assessed using simple linear regression models under the assumption of an additive genetic model. Genome-wide significance was considered at P < 10-7.

RESULTS

The MTHFR rs1801133 was the major genetic coding variant contributing to RBC folate, serum folate, and homocysteine concentrations (P = 2.28 × 10-16; P = 8.85 × 10-8, and P = 2.46 × 10-13, repsectively). It is associated with increased RBC folate (β: 0.154 per additional risk allele after log transform), decreased serum folate (β: -0.951 per additional risk allele), and increased serum homocysteine concentrations (β: 1.153 per additional risk allele). The predominant SNP associated with serum folate was rs147162222 in NTRK2 (P = 2.55 × 10-8), although that associated with homocysteine was rs77025184 located between PDE7B and LINC00271 (P = 4.91 × 10-17). For vitamin B-12, FUT2 rs1047781 was the dominant genetic variant (P = 1.59 × 10-10). The numbers of signals with a P value of <10-7 for RBC folate, serum folate, vitamin B-12, and homocysteine were 12, 18, 8, and 614, respectively.

CONCLUSIONS

This study represents the first genome-wide association study focusing on folate-related biomarkers in a Chinese preparing-for-pregnant female population. The contributions of dominent SNPs to each biomarker are partly different from other populations. The rs1801133 (C677T) in MTHFR is the predominant genetic variant contributing to RBC folate and rs1047781 (A385T) in FUT2 as the primary one explaining vitamin B-12. Notably, the intronic rs147162222 and noncoding rs77025184 are the predominant SNPs for serum folate and homocysteine, respectively.

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Affiliation(s)

Qinyu Yao Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Shanghai Key Laboratory of Birth Defects, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Xiaotian Chen Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Yi Zhang Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Hongyan Chen Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Shanghai Key Laboratory of Birth Defects, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Yalan Dou Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Wennan He Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Wei Sheng Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Shanghai Key Laboratory of Birth Defects, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Xiaojing Ma Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Shanghai Key Laboratory of Birth Defects, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Fang Liu Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Shanghai Key Laboratory of Birth Defects, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Weili Yan Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Shanghai Key Laboratory of Birth Defects, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Guoying Huang Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases (2018RU002), Chinese Academy of Medical Sciences, Beijing, China; Shanghai Key Laboratory of Birth Defects, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

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Huang X, Bao H, Ding C, Li J, Cao T, Liu L, Wei Y, Zhou Z, Zhang N, Song Y, Chen P, Jiang C, Xie L, Qin X, Zhang Y, Li J, Sun N, Tang G, Wang X, Wang H, Huo Y, Cheng X. Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy). Eur J Nutr 2024;63:1513-1528. [PMID: 38478042 PMCID: PMC11329420 DOI: 10.1007/s00394-024-03344-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 01/23/2024] [Indexed: 08/18/2024]

Affiliation(s)

Xiao Huang Department of Cardiology, The Second Affiliated Hospital, Jiangxi medical College, Nanchang University, Nanchang, China
Huihui Bao Department of Cardiology, The Second Affiliated Hospital, Jiangxi medical College, Nanchang University, Nanchang, China Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Congcong Ding Department of Cardiology, The Second Affiliated Hospital, Jiangxi medical College, Nanchang University, Nanchang, China
Junpei Li Department of Cardiology, The Second Affiliated Hospital, Jiangxi medical College, Nanchang University, Nanchang, China
Tianyu Cao Biological Anthropology, University of California Santa Barbara, Santa Barbara, CA, USA
Lishun Liu Institute of Biomedicine, Anhui Medical University, Hefei, China Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
Yaping Wei Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Ziyi Zhou Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
Nan Zhang Department of Cardiology, Peking University First Hospital, Beijing, China
Yun Song Institute of Biomedicine, Anhui Medical University, Hefei, China
Ping Chen College of Pharmacy, Jinan University, Guangzhou, China
Chongfei Jiang The Department of Nephrology, The University of Hongkong-Shenzhen Hospital, Shenzhen, China
Liling Xie National Clinical Research Study Center for Kidney Disease, The State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China
Xianhui Qin National Clinical Research Study Center for Kidney Disease, The State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China
Yan Zhang Department of Cardiology, Peking University First Hospital, Beijing, China
Jianping Li Department of Cardiology, Peking University First Hospital, Beijing, China
Ningling Sun Department of Hypertension, Heart Center, Peking University People's Hospital, Beijing, China
Genfu Tang School of Health Administration, Anhui Medical University, Hefei, China
Xiaobin Wang Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA
Hong Wang Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA
Yong Huo Department of Cardiology, Peking University First Hospital, Beijing, China
Xiaoshu Cheng Department of Cardiology, The Second Affiliated Hospital, Jiangxi medical College, Nanchang University, Nanchang, China. Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

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Liang H, Jiang J, Ren F. Relationship Between Serum HBV-RNA Levels, Sero-biochemical Indices, and Clinicopathological Parameters in Patients with Hepatitis B Virus. HEPATITIS MONTHLY 2024;24. [DOI: 10.5812/hepatmon-145421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 04/28/2024] [Accepted: 05/12/2024] [Indexed: 01/02/2025]

Luo Z, Tang K, Huang G, Wang X, Zhou S, Dai D, Yang H, Jiang W. Homocysteine concentration in coronary artery disease and severity of coronary lesions. J Cell Mol Med 2024;28:e18474. [PMID: 38896027 PMCID: PMC11187881 DOI: 10.1111/jcmm.18474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/19/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open

Grover T, Chawla K, Dessai RM, Gulati S. Fault in Our Genes: A Case of Pulmonary Thromboembolism in Young. Ann Afr Med 2024;23:234-236. [PMID: 39028172 PMCID: PMC11210736 DOI: 10.4103/aam.aam_68_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 06/01/2023] [Accepted: 06/13/2023] [Indexed: 07/20/2024] Open

Bjørke-Monsen AL, Ueland PM. Folate - a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res 2023;67:10258. [PMID: 38187793 PMCID: PMC10770645 DOI: 10.29219/fnr.v67.10258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 05/29/2022] [Accepted: 09/27/2023] [Indexed: 01/09/2024] Open

Zarembska E, Ślusarczyk K, Wrzosek M. The Implication of a Polymorphism in the Methylenetetrahydrofolate Reductase Gene in Homocysteine Metabolism and Related Civilisation Diseases. Int J Mol Sci 2023;25:193. [PMID: 38203363 PMCID: PMC10779094 DOI: 10.3390/ijms25010193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open

Mizuno T, Hoshino T, Ishizuka K, Toi S, Takahashi S, Wako S, Arai S, Kitagawa K. Hyperhomocysteinemia Increases Vascular Risk in Stroke Patients with Chronic Kidney Disease. J Atheroscler Thromb 2023;30:1198-1209. [PMID: 36436876 PMCID: PMC10499453 DOI: 10.5551/jat.63849] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 10/31/2022] [Indexed: 09/05/2023] Open

Chen J, Rees A, Coughlan CH, Goodison W, Murphy E, Chandratheva A. Ischaemic stroke with multi-focal venous and arterial thrombosis due to hyperhomocysteinemia: anabolic androgenic steroid use and MTHFR c.667 C > T variant - a case report. BMC Neurol 2023;23:167. [PMID: 37101129 PMCID: PMC10131300 DOI: 10.1186/s12883-023-03197-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/03/2023] [Indexed: 04/28/2023] Open

Abstract

BACKGROUND

Severely elevated serum homocysteine is a rare cause of ischaemic stroke and extra-cranial arterial and venous thrombosis. Several factors can lead to mild elevation of homocysteine including dietary folate and B12 deficiency, and genetic variants of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The use of Anabolic androgenic steroid (AAS) is under-reported, but increasingly linked to ischaemic stroke and can raise homocysteine levels.

CASE REPORT

We present a case of a man in his 40s with a large left middle cerebral artery (MCA) territory ischaemic stroke and combined multifocal, extracranial venous, and arterial thrombosis. His past medical history was significant for Crohn's disease and covert use of AAS. A young stroke screen was negative except for a severely elevated total homocysteine concentration, folate and B12 deficiencies. Further tests revealed he was homozygous for the methylenetetrahydrofolate reductase enzyme thermolabile variant (MTHFR c.667 C > T). The etiology of this stroke was a hypercoagulable state induced by raised plasma homocysteine. Raised homocysteine in this case was likely multifactorial and related to chronic AAS use in combination with the homozygous MTHFR c.677 C > T thermolabile variant, folate deficiency and, vitamin B12 deficiency.

CONCLUSION

In summary, hyperhomocysteinemia is an important potential cause of ischaemic stroke and may result from genetic, dietary, and social factors. Anabolic androgenic steroid use is an important risk factor for clinicians to consider, particularly in cases of young stroke with elevated serum homocysteine. Testing for MFTHR variants in stroke patients with raised homocysteine may be useful to guide secondary stroke prevention through adequate vitamin supplementation. Further studies looking into primary and secondary stroke prevention in the high-risk MTHFR variant cohort are necessary.

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Özsoy Ş, Özsoy Z, Gevrek F, Yeniova AÖ. Protective role of vitamin B12 on acetic acid induced colitis in rats. Turk J Surg 2023;39:7-16. [PMID: 37275922 PMCID: PMC10234719 DOI: 10.47717/turkjsurg.2023.5903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 12/13/2022] [Indexed: 06/07/2023]

Yao S, Chen X, Zhou Y, Xu L, Zhang Q, Bao S, Feng H, Ge W. The association between altitude and serum folate levels in Tibetan adults on the Tibetan plateau. Sci Rep 2022;12:17886. [PMID: 36284137 PMCID: PMC9596477 DOI: 10.1038/s41598-022-22968-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 10/21/2022] [Indexed: 01/20/2023] Open

Pavlik R, Hecht S, Noss U, Soldin OP, Mendu RD, Soldin SJ, Lohse P, Thaler CJ. Reduced Steroid Synthesis in the Follicular Fluid of MTHFR 677TT Mutation Carriers: Effects of Increased Folic Acid Administration. Geburtshilfe Frauenheilkd 2022;82:1074-1081. [PMID: 36186148 PMCID: PMC9525144 DOI: 10.1055/a-1791-9358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/24/2022] [Indexed: 10/27/2022] Open

Abstract

Objective To compare steroid profiles in the follicular fluid (FF) from women homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation and wildtype controls and to correlate it with the folic acid administration scheme applied at the time of oocyte retrieval. Design Retrospective single center study. Subjects and Methods Infertile patients treated by using assisted reproductive techniques were genotyped routinely for the MTHFR 677C>T mutation. In 2006 they had received folic acid supplementation doses of 400 µg daily per os. This group was designated Group-400 (n = 10). From 2008 onwards, all of our infertility patients received a daily dose of 800 µg folic acid per os. Women from this group were designated Group-800 (n = 28). FF were collected and a panel of steroid hormones (estradiol, estrone, estriol, cortisol, progesterone, 17-OH progesterone, testosterone, androstenedione, aldosterone, DHEA, and DHEA-S) was measured by isotope dilution liquid chromatography-tandem mass spectrometry employing atmospheric pressure photo ionization (APPI). Results In Group-400, the FF hormone profile confirmed a significant reduction of estradiol in homozygous 677TT carriers (0.52 ± 0.08-fold, exact p = 0.032) and for the first time also revealed significantly reduced estriol concentrations in these individuals (0.54 ± 0.05-fold, p = 0.016), as compared to wildtype controls. In Group-800, no significant differences were found for concentrations of any of the steroid hormones between homozygous 677TT carriers and wildtype controls. Conclusions The current findings support and extend previous reports on reduced concentrations of specific steroid hormones in follicular fluids of homozygous MTHFR 677C>T mutation carriers. The restoration of the FF hormone profile by elevated-dose folic acid supplementation might impact performing ART in infertile women with the MTHFR 677TT-genotype. Further adequately powered studies are necessary to verify our finding and to demonstrate the clinical effect of enhanced folic supplementation on ovarian function.

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Georgiev T, Hadzhibozheva P, Karamalakova Y, Georgieva E, Perinkadakatt F, Ilinov Z, Petkov K, Ananiev J. Therapeutic approach of glutathione/glutathione peroxidase-4 axis modulation in the light of ferroptosis. PHARMACIA 2022. [DOI: 10.3897/pharmacia.69.e87716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open

Zhang Q, Lin J, Zhang Z, Han L, Huang Q, Zhu J, Wang B, Fang X, Zheng Z, Yawalkar N, Liang J, Yan K. MTHFR Polymorphism and Folic Acid Supplementation Influence Serum Homocysteine Levels in Psoriatic Patients Treated with Methotrexate. J Clin Med 2022;11:jcm11154580. [PMID: 35956194 PMCID: PMC9369514 DOI: 10.3390/jcm11154580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 08/03/2022] [Accepted: 08/03/2022] [Indexed: 11/16/2022] Open

Nakano H, Inoue S, Minegishi Y, Igarashi A, Tokairin Y, Yamauchi K, Kimura T, Nishiwaki M, Nemoto T, Otaki Y, Sato M, Sato K, Machida H, Yang S, Murano H, Watanabe M, Shibata Y. Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema. Sci Rep 2022;12:12968. [PMID: 35902671 PMCID: PMC9334265 DOI: 10.1038/s41598-022-16767-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 07/15/2022] [Indexed: 11/15/2022] Open

Affiliation(s)

Hiroshi Nakano Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Sumito Inoue Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
Yukihiro Minegishi Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Akira Igarashi Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Yoshikane Tokairin Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Keiko Yamauchi Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Tomomi Kimura Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Michiko Nishiwaki Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Takako Nemoto Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Yoichiro Otaki Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Masamichi Sato Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Kento Sato Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Hiroyoshi Machida Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Sujeong Yang Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Hiroaki Murano Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Masafumi Watanabe Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
Yoko Shibata Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan

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Fu J, Liu Q, Zhu Y, Sun C, Duan H, Huang L, Zhou D, Wang Z, Zhao J, Li Z, Ma F, Li W, Liu H, Zhang X, Chen Y, Wang G, Du Y, Huang G. Circulating folate concentrations and the risk of mild cognitive impairment: a prospective study on the older Chinese population without folic acid fortification. Eur J Neurol 2022;29:2913-2924. [PMID: 35735052 DOI: 10.1111/ene.15474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 06/15/2022] [Accepted: 06/19/2022] [Indexed: 11/28/2022]

Abstract

BACKGROUND

The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid was not implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI.

METHODS

We performed a longitudinal analysis of 3974 participants aged ≥ 60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate-MCI association were explored via a path analysis approach.

RESULTS

Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (P for trend < 0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (P < 0.05).

CONCLUSIONS

Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.

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Affiliation(s)

Jingzhu Fu Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Qian Liu Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Yun Zhu Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Changqing Sun Neurosurgical Department of Baodi Clinical College of Tianjin Medical University, Tianjin, China
Huilian Duan Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Ling Huang Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Dezheng Zhou Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Zehao Wang Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Jing Zhao Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Zhenshu Li Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Fei Ma Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Wen Li Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Huan Liu Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Xumei Zhang Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Yongjie Chen Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Guangshun Wang Department of Tumor, Baodi Clinical College of Tianjin Medical University, Tianjin, China
Yue Du Department of Social Medicine and Health Management, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
Guowei Huang Department of Nutrition & Food Science, School of Public Health, Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China

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Li M, Chen X, Zhang Y, Chen H, Wang D, Cao C, Jiang Y, Huang X, Dou Y, Wang Y, Ma X, Sheng W, Yan W, Huang G. RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort. J Nutr 2022;152:1496-1506. [PMID: 35259272 DOI: 10.1093/jn/nxac050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/03/2022] [Accepted: 02/28/2022] [Indexed: 11/14/2022] Open

Abstract

BACKGROUND

The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health.

OBJECTIVES

This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples.

METHODS

This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia.

RESULTS

The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 μmol/L (7.48, 7.60 μmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 μmol/L (11.9, 12.2 μmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 μmol/L, 22.1% compared with 2.5%).

CONCLUSIONS

Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

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Affiliation(s)

Mengru Li Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Key Laboratory of Birth Defects, Shanghai, China
Xiaotian Chen Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Yi Zhang Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Hongyan Chen Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Dingmei Wang Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Key Laboratory of Birth Defects, Shanghai, China
Chao Cao Shanghai Key Laboratory of Birth Defects, Shanghai, China.,Institutes of Biomedical Science, Fudan University, Shanghai, China
Yuan Jiang Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Xiangyuan Huang Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Yalan Dou Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Yin Wang Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Xiaojing Ma Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Key Laboratory of Birth Defects, Shanghai, China
Wei Sheng Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Key Laboratory of Birth Defects, Shanghai, China
Weili Yan Shanghai Key Laboratory of Birth Defects, Shanghai, China.,Department of Clinical Epidemiology and Clinical Trial Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China
Guoying Huang Pediatric Heart Center, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Key Laboratory of Birth Defects, Shanghai, China.,Research Unit of Early Intervention of Genetically Related Childhood Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China

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Association of MTHFR Polymorphisms with H-Type Hypertension: A Systemic Review and Network Meta-Analysis of Diagnostic Test Accuracy. Int J Hypertens 2022;2022:2861444. [PMID: 35360528 PMCID: PMC8964216 DOI: 10.1155/2022/2861444] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 03/01/2022] [Indexed: 11/24/2022] Open

Abstract

Purpose

An association between MTHFR polymorphisms and H-type hypertension (H-HTN) has been investigated by epidemiological studies, but results have been inconsistent. Thus, a systematic assessment of the association was performed based on a literature review and pooled analysis, to provide stronger evidence on the effects of single nucleotide polymorphisms on H-HTN risk.

Methods

Three investigators independently retrieved relevant studies in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and China Biomedical Literature Database (CBM). A fixed or random effects model was selected to calculate pooled odds ratio (OR) and 95% confidence intervals (CIs). A network meta-analysis of diagnostic test and Thakkinstian's algorithm were used to select the most appropriate genetic model, along with false-positive report probability (FPRP) for noteworthy associations. All data were processed using Stata 15.0 and Meta-Disc.

Results

A total of 14 studies involving 1759 cases and 1581 controls for MTHFR were included in our meta-analysis. In a direct meta-analysis, we found that MTHFR C667T rs1801133 significantly increased the risk of H-HTN susceptibility except for an overdominant model. However, MTHFR A1298C rs1801131 polymorphism had no significant correlation with H-HTN risk. Besides, MTHFR C667T rs1801133 is a potential diagnostic biomarker for estimating H-HTN risk. The results indicated that the dominant model was an optimal diagnosis model for excluding diseases, which could reduce a missed diagnosis rate and further improve the accuracy of disease diagnosis.

Conclusion

The present result suggests that MTHFR C667T rs1801133 polymorphism is associated with H-HTN risk and may act as a promising predictive biomarker for H-HTN risk. However, further well-designed studies are warranted to confirm these results.

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Explore the Role of the rs1801133-PPARG Pathway in the H-type Hypertension. PPAR Res 2022;2022:2054876. [PMID: 35356087 PMCID: PMC8958104 DOI: 10.1155/2022/2054876] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/09/2022] [Accepted: 02/15/2022] [Indexed: 11/18/2022] Open

Abstract Both rs1801133 mutation on Methylenetetrahydrofolate reductase (MTHFR) gene and transcription factor peroxisome proliferator-activated gamma (PPARG) have been associated with plasma homocysteine (Hcy) levels and hypertension. However, their role in H-type hypertension remains unclear. In this study, we first tested the association between rs1801133 genotypes and Hcy level in H-type hypertension using clinical profiles collected from 203 patients before and after the treatment using enalapril maleate and folic acid tablets (EMFAT). Then, we constructed a literature-based pathway analysis to explore the role of the rs1801133-PPARG signaling pathway in H-type hypertension and its treatment. Although presented similar blood pressure, the patients with TT genotype of rs1801133 were much younger (

p

value <0.05) and significantly higher in Hcy levels (

x^{2} = 6.11

and

p < 0.005

) than that in the CC and CT genotype groups. Pathway analysis showed that T-allele of rs1801133 could inhibit the expression of PPARG through the downregulation of folate levels and upregulation of Hcy levels, which increased the risk of hypertension and hyperhomocysteinemia. Treatment using EMFAT led to similarly decreased Hcy levels for all patients with different genotypes (

x^{2} = 86.00

;

p < 0.36

), which may occur partially through the activation of PPARG. Moreover, even after treatment, the patients with TT genotype still presented significantly higher Hcy levels (

x^{2} = 7.87

and

p < 0.001

). Our results supported that rs1801133 mutation could play a role in H-type hypertension, which might be partially through the downregulation of PPARG. Moreover, PPARG might also be involved in treating H-type hypertension using EMFAT. Collapse

Rai V, Kumar P. Relation Between Methylenetetrahydrofolate Reductase Polymorphisms (C677T and A1298C) and Migraine Susceptibility. Indian J Clin Biochem 2022;37:3-17. [PMID: 35125689 PMCID: PMC8799834 DOI: 10.1007/s12291-021-01000-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 08/17/2021] [Indexed: 01/03/2023]

Raghubeer S, Matsha TE. Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks. Nutrients 2021;13:nu13124562. [PMID: 34960114 PMCID: PMC8703276 DOI: 10.3390/nu13124562] [Citation(s) in RCA: 105] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/07/2021] [Accepted: 12/15/2021] [Indexed: 02/06/2023] Open

Qian XL, Cao H, Zhang J, Gu ZH, Tang WQ, Shen L, Hu JL, Yao ZF, Zhang L, Tang MN, Lv XC, Zhou J, Jin XJ, Hong B, Cui ZQ, Ge JB. The prevalence, relative risk factors and MTHFR C677T genotype of H type hypertension of the elderly hypertensives in Shanghai, China: a cross-section study : Prevalence of H type hypertension. BMC Cardiovasc Disord 2021;21:376. [PMID: 34348647 PMCID: PMC8336333 DOI: 10.1186/s12872-021-02151-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 06/25/2021] [Indexed: 12/27/2022] Open

Abstract

Background

H type hypertension is defined as homocysteine (Hcy) ≥ 10 μmol/L in combination with primary hypertension. Studies demonstrated that the existence of hyperhomocysteine (HHcy) in hypertensive exacerbates the poor outcome of cardiocerebral incidents. This study was to investigate the current epidemic situation of H type hypertension and determine the risk factors in order to find intervention targets for H type hypertensives.

Methods

We conducted a cross-sectional study using cluster sampling design in Shanghai, China from July 2019 and April 2020. 23,652 patients with primary hypertension were enrolled in this study. Their medical information was recorded, and the level of Hcy concentrations and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms were detected.

Results

In total, 22,731 of 23,652 patients were recorded. The mean age was 68.9 ± 8.6 y and 43% were men. 80.0% of the enrolled patients had H type hypertension. The frequency of allele T was 40.9%, and the proportions of the CC, CT, and TT genotypes were 36.1%, 46.0%, and 17.9%, respectively. Compared with the TT genotype, the plasma Hcy concentration levels were lower in patients with the CC/CT genotype (18.96 ± 13.48 μmol/L vs. 13.62 ± 5.20/14.28 ± 5.36, F = 75.04, p < 0.01). The risk for H type hypertension was higher in elderly people. Men had ~ 5.55-fold odds of H type hypertension compared with women. Patients with CT genotype and TT genotype had ~ 1.36- and ~ 2.76-fold odds of H type hypertension compared with those with CC genotype, respectively. Smoking and diabetes were not significantly associated with H type hypertension.

Conclusions

The prevalence of H type hypertension in patients with primary hypertension was 80.0%, which was higher than the 75% found in prior report in China. Age, gender, and MTHFR C677T polymorphisms rather than smoking and diabetes were independently associated with H type hypertension.

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Affiliation(s)

Xiao-Lin Qian Department of Cardiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, QingPu District Central Hospital Shanghai, Shanghai, China
Hong Cao Department of Cardiology, QingPu District Jinze Community Health Center, Shanghai, China
Jun Zhang Department of Cardiology, QingPu District Xujing Community Health Center, Shanghai, China
Zhi-Hui Gu Department of Cardiology, QingPu District Zhujiajiao Community Health Center, Shanghai, China
Wei-Qin Tang Department of Cardiology, QingPu District Xianghuaqiao Community Health Center, Shanghai, China
Lei Shen Department of Cardiology, QingPu District Yingpu Community Health Center, Shanghai, China
Jia-Lu Hu Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China
Zhi-Feng Yao Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China
Lei Zhang Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China
Min-Na Tang Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China
Xu-Cheng Lv Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China
Jun Zhou Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China
Xue-Juan Jin Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China
Bin Hong Department of Cardiology, Shanghai Zhujiajiao People's Hospital, Shanghai, China.
Zhao-Qiang Cui Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China.
Jun-Bo Ge Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China.

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Morales R, Lledó B, Ortiz JA, Cascales A, Codina H, Rodríguez-Arnedo A, Llácer J, Bernabeu A, Bernabeu R. Methylenetetrahydrofolate reductase gene polymorphisms are not associated with embryo chromosomal abnormalities and IVF outcomes. Syst Biol Reprod Med 2021;67:270-280. [PMID: 34053384 DOI: 10.1080/19396368.2021.1923861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]

Abstract

The aim of our study was to investigate the effect of maternal and embryo MTHFR C677T and A1298C polymorphisms on embryo aneuploidies and mosaicism and the correlation between these genetic variants in transferred euploid embryos and IVF outcomes. MTHFR genotype was analyzed in 77 women who performed an IVF/ICSI cycle with PGT-A. Moreover, to evaluate the effect of embryo MTHFR polymorphisms on embryo aneuploidies and mosaicism, the MTHFR genotype was analyzed in 191 biopsied embryos from the PGT-A cycles of these patients. Additionally, 218 DNA samples from trophectoderm biopsies belonging to a different group of patients were also genotyped. MTHFR polymorphisms were analyzed in a total amount of 409 trophectoderm samples. The main parameters analyzed were embryo aneuploidy and mosaicism rates. Finally, the IVF outcomes of 241 single euploid embryo transfers were assessed and compared between different MTHFR embryo genotypes. The aneuploidy rates were similar in embryos from homozygous normal women and women with at least one mutated allele (54.7% vs. 30.2% in 677C>T and 37.8% vs. 42.7% in 1298A>C). Furthermore, no differences were observed in the mosaicism rate (24.0% vs. 13.8% in 677C>T and 17.1% vs. 17.3% in 1298A>C). A similar analysis was performed, taking into account the embryo genotype results. No differences in aneuploidy rate were observed between the study groups. The only significant difference was the mosaicism rate among 677C>T genotype (13.5% in 677CC group vs. 5.4% in 677CT/TT; p = 0.019). Implantation rate, biochemical and clinical miscarriage rates, and ongoing pregnancy rate were compared between different embryo genotypes, and no statistically significant differences were found. In conclusion, the maternal MTHFR genotype did not influence embryo chromosomal abnormalities. Moreover, the embryo MTHFR genotype was not associated with embryo aneuploidy or IVF outcomes such as implantation, pregnancy loss, and ongoing pregnancy when euploid embryos were transferred.Abbreviations: MTHFR: methylenetetrahydrofolate reductase; IVF: in vitro fertilization; PGT-A: preimplantation genetic testing for aneuploidies; SAM: S-adenosyl methionine; SNP: single nucleotide polymorphism; SPSS: Statistical Package for Social Sciences; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; hCG: human chorionic gonadotropin; PBS: phosphate buffered saline; CGH: comparative genomic hybridization; NGS: next generation sequencing.

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Liu YT, Lin CC, Wang L, Nfor ON, Hsu SY, Lung CC, Tantoh DM, Chang HR, Liaw YP. Peripheral Vascular Disease Susceptibility Based on Diabetes Mellitus and rs17367504 Polymorphism of the MTHFR Gene. Diabetes Metab Syndr Obes 2021;14:2381-2388. [PMID: 34079316 PMCID: PMC8165095 DOI: 10.2147/dmso.s309242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 04/28/2021] [Indexed: 11/29/2022] Open

Abstract

PURPOSE

Peripheral vascular disease (PVD) is a life-threatening condition affecting the lower extremities. Common risk factors include type 2 diabetes (T2D), hypertension, dyslipidemia, smoking, and older age. There is a little-documented research on the genetic basis of the disease in Taiwan. We examined the impact of T2D and the blood pressure-associated rs17367504 variant of the Methylenetetrahydrofolate reductase (MTHFR) gene on PVD risk.

MATERIALS AND METHODS

In this population-based association study, we linked data from 8992 participants in Taiwan Biobank (TWB) to their medical records in the National Health Insurance Research Database (NHIRD). Participants were 30 to 70 years old at recruitment and included those assessed between 2008 and 2015. We tested for association of PVD with rs17367504 and T2D using multiple logistic regression models. The rs17367504 variant was assessed using the Axiom-Taiwan Biobank Array Plate (TWB chip: Affymetrix, Inc., Santa Clara, CA, USA).

RESULTS

Among cases with T2D (n = 1294), 158 (12.21%) were identified with PVD. T2D was associated with PVD (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.21-1.91; p<0.001) whereas rs17367504 variant was not (OR, 0.96; CI, 0.76-1.21; p = 0.728 in AG/GG compared to AA homozygotes). However, T2D and rs17367504 had an interactive effect on PVD (p for interaction = 0.0076). Results from our stratified analyses displayed OR of 1.75 (CI, 1.35-2.26; p<0.001) in AA individuals with DM and 0.94 (CI, 0.56-1.58; p = 0.811) in AG+GG individuals with T2D. Using the AA genotype and no T2D as the reference group, the respective OR of PVD was 1.77 (CI, 1.38-2.28; p<0.001) in AA individuals with T2D; 1.18 (CI, 0.91-1.55; p = 0.215) in AG+GG individuals with no T2D, and 1.03 (CI, 0.66-1.60; p = 0.892) in AG+GG individuals with T2D .

CONCLUSION

We found that type 2 diabetes was associated with increased risk of peripheral vascular disease, particularly in AA genotype carriers of the rs17367504 variant in Taiwan.

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Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis. J Assist Reprod Genet 2021;38:2237-2249. [PMID: 34032987 DOI: 10.1007/s10815-021-02236-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 05/12/2021] [Indexed: 10/21/2022] Open

Abstract

OBJECTIVE

Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the results remain controversial. The aim of the systematic review and meta-analysis was to evaluate the effect of MTHFR polymorphism on COS outcomes.

METHODS

PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 2, 2020. COS clinical outcomes based on gene polymorphisms were included. Two reviewers independently extracted the data. The primary outcome was the number of oocytes retrieved. The secondary outcomes were the number of metaphase II (MII) oocytes, stimulation duration, basal follicle-stimulating hormone (FSH) level, FSH dosage, positive pregnancy test, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Meta-analysis was performed using a fixed-effect model or random-effect model with Review Man 5.3.5. Mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for continuous outcomes. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale.

RESULTS

Eleven studies were included in the systematic review, and seven studies with 2015 participants were included in the meta-analysis. Basal FSH level was significantly lower in CC homozygotes than TT homozygotes (four studies, 867 participants, MD - 0.54, 95%CI - 0.85 to - 0.23, P = 0.0006; I² = 0%) of MTHFR (rs1801133). FSH dose was significantly fewer in CC homozygotes compared with CT heterogeneous (three studies, 949 participants, MD - 75.78, 95%CI - 135.23 to - 16.33, P = 0.01; I² = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I² = 42%). Differences in the oocytes retrieved and stimulation duration were insignificant. Gene variants on MTHFR (rs1801133) and MTHFR (rs1801131) were reported in ongoing pregnancy rate, clinical pregnancy rate, and live birth rate.

CONCLUSION

Studies to date indicate that polymorphisms of MTHFR could influence basal FSH level and FSH dose. The results could be useful to promote clinical practice on COS protocols. Further studies are needed to evaluate the clinical relevance of the multigene combination on COS.

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Ota K, Takahashi T, Han A, Damvaeba S, Mizunuma H, Kwak-Kim J. Effects of MTHFR C677T polymorphism on vitamin D, homocysteine and natural killer cell cytotoxicity in women with recurrent pregnancy losses. Hum Reprod 2021;35:1276-1287. [PMID: 32478379 DOI: 10.1093/humrep/deaa095] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 03/17/2020] [Indexed: 12/26/2022] Open

Abstract

STUDY QUESTION

Is there any relationship between vitamin D [25 (OH) vitamin D], total plasma homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in women with recurrent pregnancy losses (RPL)?

SUMMARY ANSWER

Women with MTHFR 677TT (homozygous mutation, TT) genotype have significantly lower vitamin D levels, higher homocysteine and natural killer (NK) cell cytotoxicities than those of women with MTHFR 677CC (wild type, CC) and 677CT (heterozygous mutation, CT) genotypes.

WHAT IS KNOWN ALREADY

Vitamin D insufficiency, MTHFR C677T polymorphism and hyperhomocysteinemia have been reported as risk factors for RPL. However, the relationship between these risk factors is not known in this population.

STUDY DESIGN, SIZE, DURATION

This is a retrospective cross-sectional study, including 837 women with RPL, who were enrolled in Reproductive Medicine and Immunology, Chicago Medical School, between 2012 and 2017.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Women with two or more RPL prior to 20 weeks of gestation were included. To investigate whether the MTHFR C677T polymorphism affects the levels of homocysteine and vitamin D as well as immune parameters in women with RPL, biochemical data, such as plasma total homocysteine and serum vitamin D levels, and immune parameters, including NK cell cytotoxicity, were analyzed by MTHFR C677T genotype (CC, CT and TT).

MAIN RESULTS AND THE ROLE OF CHANCE

The serum level of vitamin D in TT was significantly lower when compared with those of CT (P = 0.001) and CC (P = 0.003), while the level of homocysteine in TT was significantly higher than those in CT (P = 0.01) and CC (P = 0.01). NK cytotoxicity in TT was significantly higher than that of CC (P = 0.04) but not CT (P = 0.09). There was a significant negative correlation between the levels of vitamin D and homocysteine in TT (r = -0.357, P < 0.01). In multivariate analysis, vitamin D insufficiency (<30 ng/ml) was an independent risk factor for hyperhomocysteinemia (adjusted odds ratio 1.89, 95% CI 1.41-2.52).

LIMITATIONS, REASONS FOR CAUTION

The study was retrospective and included only women with RPL but not healthy fertile controls. In addition, folic acid, vitamin B6 and B12 intake, which could modify the level of homocysteine and vitamin D, were not investigated. Thus, a considerable part of women might have folic acid and vitamin D supplementation and prenatal vitamin pills, and there are probable confounders in this study associated with unrestricted vitamin supplementation. Therefore, the findings should be carefully interpreted and applied to RPL women with MTHFR gene polymorphism.

WIDER IMPLICATIONS OF THE FINDINGS

The findings attained in this analysis regarding the MTHFR polymorphism and its relationship with vitamin D, homocysteine and NK cytotoxicity may aid in uncovering the underlying etiology and mechanism for RPL. The study highlights an interplay between nutrition and immune responses in RPL.

STUDY FUNDING/COMPETING INTEREST(S)

No external funding was received for this study. None of the authors have any conﬂict of interest to declare.

TRIAL REGISTRATION NUMBER

N/A.

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Dick-Guareschi J, Fontana JC, Sanseverino MTV, Kubaski F, Sekine L, Mesquita NF, Onsten TGH, Leistner-Segal S. Prevalence of thrombophilia-associated genetic risk factors in blood donors of a regional hospital in southern Brazil. Hematol Transfus Cell Ther 2021;44:379-385. [PMID: 33775585 PMCID: PMC9477773 DOI: 10.1016/j.htct.2021.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 01/02/2021] [Accepted: 01/27/2021] [Indexed: 11/20/2022] Open

Marques M, Alves F, Leitão M, Rodrigues C, Ferreira JT. Methylenetetrahydrofolate reductase polymorphisms as risk factors for retinal venous occlusive disease: A literature review. Eur J Ophthalmol 2021;31:884-891. [PMID: 33715478 DOI: 10.1177/11206721211000647] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]

Bagher AM, Young AP, Neamatallah T, Al-Amoudi RM, Bagher SM, Denovan-Wright EM. Prevalence of methylenetetrahydrofolate reductase gene polymorphisms (C677T, and A1298C) among Saudi children receiving dental treatment. Ann Saudi Med 2021;41:1-7. [PMID: 33550905 PMCID: PMC7868620 DOI: 10.5144/0256-4947.2021.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 12/23/2020] [Indexed: 11/22/2022] Open

Abstract

BACKGROUND

Methylenetetrahydrofolate reductase, the encoded by the MTHFR gene, plays a crucial role in converting the amino acid homocysteine to methionine. Two polymorphisms of the MTHFR gene, C677T and A1298C, reportedly reduce enzyme activity, resulting in hyperhomocysteinemia. Patients with C677T and A1298C polymorphisms may be at higher risk for developing abnormal hyperhomocysteinemia, which has been linked to catastrophic neurological including fatal outcomes.

OBJECTIVE

Determine the prevalence of the MTHFR gene variants C677T and A1298C among pediatric dental patients treated at King Abdulaziz University Hospital.

DESIGN

Cross-sectional.

SETTING

Clinics of pediatric dentistry department.

SUBJECTS AND METHODS

Healthy Saudi children 6-12 years old with no known allergies were screened for eligibility between May and December 2019. A single investigator collected saliva samples. The MTHFR C677T and A1298C polymorphisms were analyzed using polymerase chain reaction and restriction fragment length polymorphism.

MAIN OUTCOME MEASURE

The prevalence of MTHFR gene variants (C677T and A1298C) among the subjects.

SAMPLE SIZE

138.

RESULTS

MTHFR C677T polymorphism was present in 36.2% of the sample and 90.0% of children carrying this allele were heterozygotes. MTHFR A1298C polymorphism was present in 91.3% of the sample and 77.0% of the children carrying this allele were heterozygotes. No linkage disequilibrium between MTHFR C677T and MTHFR A1298C was observed within this sample.

CONCLUSIONS

Our study found a high frequency of the MTHFR A1298C genotype, which was substantially more abundant than expected based on a Hardy-Weinberg distribution. Therefore, caution is advised in using N2O in Saudi children as the increased prevalence of this MTHFR allele may increase the incidence of serious adverse effects among these children.

LIMITATIONS

Further studies are recommended with a larger sample size from randomly selected hospitals from different regions of Saudi Arabia.

CONFLICT OF INTEREST

None.

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Sotelo-Orozco J, Abbeduto L, Hertz-Picciotto I, Slupsky CM. Association Between Plasma Metabolites and Psychometric Scores Among Children With Developmental Disabilities: Investigating Sex-Differences. Front Psychiatry 2020;11:579538. [PMID: 33414730 PMCID: PMC7783080 DOI: 10.3389/fpsyt.2020.579538] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 11/30/2020] [Indexed: 12/27/2022] Open

Abstract

Background: Developmental disabilities are defined by delays in learning, language, and behavior, yet growing evidence has revealed disturbances in metabolic systems that may also be present. Little is known about whether these metabolic issues contribute to the symptoms or severity of these disabilities, or whether sex plays a role in these associations, given that boys are disproportionately affected by some developmental disabilities. Here we sought to investigate the correlation between psychometric scores, sex, and the plasma metabolome. Methods: The plasma metabolomes of children with autism spectrum disorder (ASD; n = 167), idiopathic developmental delay (i-DD; n = 51), Down syndrome (DS; n = 31), and typically developing controls (TD; n = 193) were investigated using NMR spectroscopy. Spearman rank correlations and multiple linear regression models (adjusted for child's neurodevelopmental diagnosis, child's sex, child's age, child's race/ethnicity, maternal age at child's birth, and parental homeownership) were used to examine the association between plasma metabolites and sex in relation to psychometric measures of cognitive skills, adaptive behavior, and maladaptive behavior in our study population. Results: Higher levels of metabolites involved in cellular energy and mitochondrial function among children with ASD (fumarate and cis-aconitate), DS (lactate), and TD (pyruvate) are associated with poorer cognitive and adaptive subscales. Similarly, higher o-acetylcarnitine associated with deficits in cognitive subscales among all DS cases and TD boys, and carnitine correlated with increased maladaptive behavior among girls with ASD and girls with DS. Among children with DS, elevated myo-inositol, ornithine, and creatine correlated with poorer scores across several subscales. Even among TD cases, elevated 3-hydroxybutyrate correlated with decreased receptive language. In contrast, higher levels of glutamate were associated with better socialization skills among ASD cases. Even after adjusting for the child's neurodevelopmental diagnosis, sex, and other possible confounders, key metabolites including glycolysis metabolites (lactate and pyruvate), ketone bodies (3-hydroxybutyrate and acetoacetate), TCA cycle metabolites (cis-aconitate and fumarate), as well as ornithine were associated with deficits in multiple domains of cognitive function, adaptive skills, and aberrant behaviors. Conclusions: Our results highlight that some plasma metabolites may relate to specific functional subdomains within cognitive, adaptive, and behavioral development with some variation by diagnosis and sex.

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Niforou A, Konstantinidou V, Naska A. Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes-A Narrative Review of the Case of Vitamins. Front Nutr 2020;7:558598. [PMID: 33335908 PMCID: PMC7736113 DOI: 10.3389/fnut.2020.558598] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 11/03/2020] [Indexed: 12/17/2022] Open

Abstract

Recent advances in the field of nutrigenetics have provided evidence on how genetic variations can impact the individuals' response to dietary intakes. An objective and reliable assessment of dietary exposures should rely on combinations of methodologies including frequency questionnaires, short-term recalls or records, together with biological samples to evaluate markers of intake or status and to identify genetic susceptibilities. In an attempt to present current knowledge on how genetic fingerprints contribute to an individual's nutritional status, we present a review of current literature describing associations between genetic variants and levels of well-established biomarkers of vitamin status in free-living and generally healthy individuals. Based on the outcomes of candidate gene, genome-wide-association studies and meta-analyses thereof, we have identified several single nucleotide polymorphisms (SNPs) involved in the vitamins' metabolic pathways. Polymorphisms in genes encoding proteins involved in vitamin metabolism and transport are reported to have an impact on vitamin D status; while genetic variants of vitamin D receptor were most frequently associated with health outcomes. Genetic variations that can influence vitamin E status include SNPs involved in its uptake and transport, such as in SCAR-B1 gene, and in lipoprotein metabolism. Variants of the genes encoding the sodium-dependent vitamin C transport proteins are greatly associated with the body's status on vitamin C. Regarding the vitamins of the B-complex, special reference is made to the widely studied variant in the MTHFR gene. Methodological attributes of genetic studies that may limit the comparability and interpretability of the findings are also discussed. Our understanding of how genes affect our responses to nutritional triggers will enhance our capacity to evaluate dietary exposure and design personalized nutrition programs to sustain health and prevent disease.

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Han LJ, He XF, Ye XH. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and male infertility risk: An updated meta-analysis. Medicine (Baltimore) 2020;99:e23662. [PMID: 33371103 PMCID: PMC7748209 DOI: 10.1097/md.0000000000023662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 11/07/2020] [Indexed: 11/26/2022] Open

Abstract

BACKGROUND

18 previous meta-analyses have been published on the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with male infertility risk. However, results of the previous meta-analyses were still inconsistent. Moreover, their meta-analyses did not assess false-positive report probabilities except one study. Furthermore, many new studies have been published, and therefore an updated meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues.

OBJECTIVES

To determine the association between MTHFR C677T and A1298C polymorphisms and male infertility risk.

METHODS

Crude odds ratios and their 95% confidence intervals were used to assess the association between MTHFR C677T and A1298C polymorphisms and male infertility risk. We used the Bayesian false discovery probability (BFDP) to assess the credibility of statistically significant associations.

RESULTS

Fifty-nine studies were included concerning the MTHFR C677T and 28 studies were found on the MTHFR A1298C with male infertility risk. Overall, the MTHFR C677T was associated with increased male infertility risk in overall populations, Africans, East Asians, West Asians, South Asians, azoospermia, and Oligoasthenoteratozoospermia (OAT). In further sensitivity analysis and BFDP test, the positive results were only considered as "noteworthy" in the overall population (TT vs CC: BFDP = 0.294, CT + TT vs CC: BFDP = 0.300, T vs C: BFDP = 0.336), East Asians (TT vs CC: BFDP = 0.089, TT vs CT + CC: BFDP = 0.020, T vs C: BFDP < 0.001), West Asians (TT vs CC: BFDP = 0.584), hospital-based studies (TT vs CC: BFDP = 0.726, TT vs CT + CC: BFDP = 0.126), and OAT (TT vs CT + CC: BFDP = 0.494) for MTHFR C677T. In addition, a significantly increased male infertility risk was found in East Asians and population-based studies for MTHFR A1298C. However, we did not find that the positive results were considered as "noteworthy" in the overall and all subgroup analyses for MTHFR A1298C.

CONCLUSIONS

In summary, this study indicates that the MTHFR C677T is associated with increased male infertility risk in East Asians, West Asians, and OAT. No significant association was observed on the MTHFR A1298C with male infertility risk.

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Analysis OF C677T polymorphism in methylene tetrahydrofolate reductase (MTHFR) gene as a risk factor for congenital talipes equino varus (CTEV). J Clin Orthop Trauma 2020;15:33-36. [PMID: 33717913 PMCID: PMC7920128 DOI: 10.1016/j.jcot.2020.11.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 11/02/2020] [Accepted: 11/06/2020] [Indexed: 11/23/2022] Open

Huang LQ, Wu CX, Wei HQ, Xu G. Clinical characteristics of H-type hypertension and its relationship with the MTHFR C677T polymorphism in a Zhuang population from Guangxi, China. J Clin Lab Anal 2020;34:e23499. [PMID: 32790014 PMCID: PMC7676193 DOI: 10.1002/jcla.23499] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/23/2020] [Accepted: 07/15/2020] [Indexed: 12/26/2022] Open

Fernández-Vega B, Álvarez L, García M, Artime E, Diñeiro Soto M, Nicieza J, Vega JA, González-Iglesias H. Association Study of MTHFR Polymorphisms with Nonarteritic Anterior Ischemic Optic Neuropathy in a Spanish Population. Biomed Hub 2020;5:34-46. [PMID: 32775330 DOI: 10.1159/000505431] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 12/16/2019] [Indexed: 11/19/2022] Open

Abstract

Introduction

Nonarteritic anterior ischemic optic neuropathy (NAION), painless loss of central and/or peripheral vision, is a multifactorial disease caused by insufficient blood flow through the posterior ciliary arteries to the optic nerve head. Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene, triggering hyperhomocysteinemia as a consequence of a decreased activity of the codified enzyme, have been considered to be among the risk factors of NAION.

Objective

The main aim was to study the association of the most common MTHFR genetic polymorphisms C677T and A1298C with NAION in a Spanish population.

Methods

In this case-control study, the association of the most common MTHFR polymorphisms was investigated in 94 unrelated native Spanish patients diagnosed with NAION and 204 healthy controls. Two single nucleotide polymorphisms located in the MTHFR gene, C677T (rs1801133) and A1298C (rs1801131), were analyzed by DNA sequencing and TaqMan assays.

Results

The allelic and genotypic frequencies of the MTHFR variants obtained in the NAION group were not significantly different when compared with the control group. A higher frequency of the C677T/A1298C genotype, codifying the nonmutated MTHFR form, was obtained in control subjects (11.27%) compared to NAION patients (4.26%), suggesting a protective effect of the wild-type protein, although this result was not conclusive considering the obtained confidence interval (CI) (95% CI: 0.13-1.06). Study of additional clinical factors including hypertension, diabetes mellitus, and dyslipidemia showed no association with a higher risk of NAION. Conversely, the clinical history of heart or cerebrovascular diseases was significantly higher in NAION patients compared to controls. Over the world, risk variants of the MTHFR gene are highly frequent, excluding African black populations, indicating a racial influence.

Conclusions

The MTHFR variants did not significantly increase the risk of suffering from NAION. However, considering that individuals with at least one of the risk variants have the MTHFR enzyme with decreased activity, it cannot be ruled out that these mutations are relevant for the development of NAION in a subgroup of the population with other specific characteristics. These may include high plasma levels of homocysteine along with nutritional deficiencies including low folate or vitamin B12 and the combination of systemic and local risk factors.

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Embryonic MTHFR contributes to blastocyst development. J Assist Reprod Genet 2020;37:1807-1814. [PMID: 32767205 DOI: 10.1007/s10815-020-01898-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 07/20/2020] [Indexed: 10/23/2022] Open

Case Report: Homozygous C677T MTHFR Gene Mutation in Male with Hypogonadism. Case Rep Endocrinol 2020. [DOI: 10.1155/2020/6945124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open

Peng X, Zhou Y, Wu X, Wang X, Bai H, Li Y, Wang Z, Chen X, Wang Y. Association of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of carotid atherosclerosis: a cross-sectional analysis of 730 Chinese Han adults in Chongqing. BMC Cardiovasc Disord 2020;20:222. [PMID: 32404177 PMCID: PMC7222312 DOI: 10.1186/s12872-020-01505-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 05/03/2020] [Indexed: 03/06/2023] Open

Abstract

BACKGROUND

Uncertainty still remains on the correlation of methylenetetrahydrofolate reductase (MTHFR) variant C677T with risk of carotid atherosclerosis (CAS), and there is a lack of reports on C677T/MTHFR in the Asian population. The association of C677T/MTHFR polymorphisms with CAS in the Chinese Han population in Chongqing was investigated in the present study.

METHODS

Subjects (n = 730, 214 females and 516 males, Han ethnicity) who provided an informed consent were randomly selected from the general population of Chongqing, China. Polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing genotyping assays were used to determine the MTHFR genotypes. The atherosclerosis index of the intima-media thickness (IMT) was measured by high-resolution ultrasound to evaluate the CAS. Less than 1.0 mm was considered as normal for IMT, 1.0-1.5 mm was considered as thickening, and ≥ 1.5 mm and a local bulge thickened in the lumen was considered as CAS. According to the carotid ultrasonography results, these subjects were divided into two groups: CAS-group (IMT ≥ 1.0 mm) and control group (IMT < 1.0 mm).

RESULTS

The frequency of C/T heterozygotes, T/T homozygotes genotype was significantly higher in the subjects with CAS (62% vs. 36.9%; 16.2% vs. 9.5%; 47.2% vs. 27.9%, P < 0.05), while the frequency of C/C homozygotes and C allele was significantly lower (21.8% vs. 53.7%; 52.8% vs. 72.1%, P < 0.05), when compared to the control group. The risk of CAS was higher for subjects with C/T heterozygotes and T/T homozygotes (OR = 4.06, 95% CI: 2.76-5.98, P < 0.001 and OR = 3.14, 95% CI: 1.73-5.69, P < 0.001, respectively), when compared to the subjects with the C/C genotype. In the model 1 (CT + TT versus CC), C677T/MTHFR was significantly associated with the prevalence of CAS, and the all adjusted OR values for CAS were 3.87 (95% CI, 2.67 to 5.62) in all, 17.18 (95% CI, 7.27 to 40.49) in women and 2.57 (95% CI, 1.65 to 3.99) in men after adjusting for potential confounding factors.

CONCLUSIONS

The present study suggests that a mutation in the methylenetetrahydrofolate reductase gene is a risk factor of CAS in the Chinese Han population.

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Okawa A, Hayashi M, Inagaki J, Okajima T, Tamura T, Inagaki K. Novel method for l-methionine determination using l-methionine decarboxylase and application of the enzyme for l-homocysteine determination. Biosci Biotechnol Biochem 2020;84:927-935. [DOI: 10.1080/09168451.2020.1715781] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]

Combined effect of polymorphisms of MTHFR and MTR and arsenic methylation capacity on developmental delay in preschool children in Taiwan. Arch Toxicol 2020;94:2027-2038. [DOI: 10.1007/s00204-020-02745-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 04/08/2020] [Indexed: 12/14/2022]

Hou J, Zhong Z, Deng Q, Lin L, Zeng X. The role of MTHFR C677T and ALDH2 Glu504Lys polymorphism in acute coronary syndrome in a Hakka population in southern China. BMC Cardiovasc Disord 2020;20:127. [PMID: 32160861 PMCID: PMC7066809 DOI: 10.1186/s12872-020-01410-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 03/02/2020] [Indexed: 01/12/2023] Open

Abstract

Background

Acute coronary syndrome (ACS) is the most serious type of coronary heart disease and is a global medical burden. The pathogenesis of ACS is very complex and still poorly understood. Epidemiologic studies have revealed that the manifestation of ACS are the results of the interactions between multiple environmental and genetic factors. The present study aimed to investigate the role of polymorphisms of MTHFR C677T and ALDH2 Glu504Lys as risk factors for ACS in a Hakka population in southern China.

Methods

Between September 1, 2015 and October 31, 2017, a total of 1957 individuals, including 860 ACS patients and 1097 controls were recruited. Blood samples were collected and genotypes were determined by DNA microarray chip method and direct sequencing method.

Results

For the MTHFR C677T polymorphism, frequencies of CC, CT, and TT genotypes were 53.60% versus 55.33, 39.53% versus 38.65 and 6.86% versus 6.02% in patients with ACS versus controls, respectively(p > 0.05). The differences in genotype frequencies between the ACS patients and controls in the three genetic model were not statistically significant. For the ALDH2 Glu504Lys polymorphism, the frequencies of ALDH2*1*1, ALDH2*1*2, and ALDH2*2*2 genotypes were 48.72, 42.67 and 8.6% in the ACS patients, respectively, while these were 53.33, 39.11 and 7.57% in the controls, respectively, showing no significant difference in the distribution of the ALDH2 genotype between the groups. Using the wild genotype ALDH2*1*1 as reference, relative risk analysis revealed a slightly increased risk for ACS in individuals with the ALDH2*1*2 plus ALDH2*2*2 genotypes (odds ratio (OR) = 1.203, 95% confidence interval (CI) = 1.006–1.438, p = 0.043). In a multivariate logistic regression model, even after adjusting for potential covariates, the association between ALDH2 *2 allele and ACS remained significant (OR = 1.242, 95% CI = 1.045–1.561, p = 0.038).

Conclusions

We present findings regarding the possible clinical impact of the ALDH2*2 variant on ACS patients in a Hakka population in southern China and our findings might help to stratify the high-risk ACS patients and implement appropriate strategies for this genetic subpopulation to ultimately guide the precision preventive procedures in the future.

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Affiliation(s)

Jingyuan Hou Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People's Republic of China. .,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, People's Republic of China. .,Guangdong Provincial Engineering and Technological Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, 514031, People's Republic of China.
Zhixiong Zhong Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, People's Republic of China.,Guangdong Provincial Engineering and Technological Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, 514031, People's Republic of China.,Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, 514031, People's Republic of China
Qiaoting Deng Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People's Republic of China.,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, People's Republic of China.,Guangdong Provincial Engineering and Technological Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, 514031, People's Republic of China
Lifang Lin Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People's Republic of China.,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, People's Republic of China.,Guangdong Provincial Engineering and Technological Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, 514031, People's Republic of China
Xing Zeng Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People's Republic of China.,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, People's Republic of China.,Guangdong Provincial Engineering and Technological Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, 514031, People's Republic of China

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Homocysteine, the methylenetetrahydrofolate reductase 677C>T polymorphism and hypertension: effect modifiers by lifestyle factors and population subgroups. Br J Nutr 2020;124:69-79. [PMID: 32127061 DOI: 10.1017/s0007114520000793] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Abstract

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18-75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association (β standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype-hypertension association was confined to adults aged ≤50 years.

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Rigatto C, Parfrey PS. Homocysteine and Cardiovascular Risk in Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686080002000201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open

Urquhart BL, House AA. Assessing Plasma Total Homocysteine in Patients with End-Stage Renal Disease. Perit Dial Int 2020. [DOI: 10.1177/089686080702700502] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open

Nagarajan H, Narayanaswamy S, Vetrivel U. Mutational landscape screening of methylene tetrahydrofolate reductase to predict homocystinuria associated variants: An integrative computational approach. Mutat Res 2020;819-820:111687. [DOI: 10.1016/j.mrfmmm.2020.111687] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 12/24/2019] [Accepted: 01/03/2020] [Indexed: 04/07/2023]