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Paraoxonase 1 (PON1) gene Q192R polymorphism in patients with vitiligo. JOURNAL OF SURGERY AND MEDICINE 2022. [DOI: 10.28982/josam.1060981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background/Aim: Vitiligo is a prevalent inflammatory illness that can affect the skin and mucosal surfaces and is characterized by patchy loss of skin pigmentation. Paraoxonase1 (PON1) is an esterase enzyme with antioxidant properties that binds to high-density lipoproteins. We examined whether the PON1 gene Q192R polymorphism is a risk factor for vitiligo among Turkish people.
Methods: The study included 70 controls and 60 vitiligo cases. Polymerase chain reaction and the restriction fragment length polymorphism technique were used to genotype the PON1 gene Q192R polymorphism.
Results: PON1 gene Q192R genotype distribution was 66.7% QQ, 33.3% QR, and 0% RR in the vitiligo and 81.4% QQ, 18.6% QR, and 0% RR in the control (P = 0.05). When vitiligo patients were compared with controls, the prevalence of the PON1 QR genotype was substantially higher and was linked to a 2.19-fold greater risk of developing vitiligo (odds ratio: 2.19, 95% confidence interval (CI): 0.97–4.91).
Conclusion: These findings imply that Q192R polymorphisms in the PON-1 gene may be linked to vitiligo in the Turkish population. The PON1 QR genotype may be a major genetic risk factor for vitiligo susceptibility and progression. Further studies with larger populations should more thoroughly clarify the association.
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Genetic associations and serum paraoxonase levels with atherosclerosis in western Iranian patients. Mol Biol Rep 2020; 47:5137-5144. [PMID: 32567023 DOI: 10.1007/s11033-020-05585-2] [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: 03/16/2020] [Accepted: 06/11/2020] [Indexed: 12/20/2022]
Abstract
The oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays a pivotal role in the initiation and progression of atherosclerosis which is a complex and progressive disorder. Paraoxonase1 (PON1), which is required for lipid metabolism, is believed to protect LDL from oxidation. The relationship between PON1 gene Leusin55Methionin (L55M) and Glutamine192Arginine (Q192R) polymorphisms in western Iranians with atherosclerosis and its association with enzyme activity and oxidized low-density lipoprotein (oxLDL) were examined in the present study. In this study, blood specimens were collected from 145 healthy individuals and 154 patients with atherosclerosis proven by angiography referred to Shahid Madani Hospital, Khorramabad, Iran. Genomic deoxy ribonucleic acid (DNA) was extracted from whole blood. For all the subjects, restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was carried out for the detection of L55M and Q192R polymorphisms. PON1 enzyme activity and the level of oxLDL were also evaluated. There was a 3.114-fold increase in the risk of developing atherosclerosis in the subjects presenting the PON1L55M, MM genotype compared to those with the LL genotype (OR 3.114; 95% CI 1.412-6.870). PON1Q192R polymorphism in the PON1 gene was not associated with atherosclerosis. Patients with atherosclerosis had significantly higher oxLDL and reduced PON1 enzyme activity (P < 0.05) compared to the controls. There was no association between the type of genotype, enzyme activity, and oxLDL level. It has been concluded that PON1L55M polymorphism and MM genotype are associated with an increased risk of coronary artery disease (CAD) in Iranian patients with atherosclerosis. We did not find any relationship between PON1Q192R polymorphism and atherosclerosis.
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Kaur S, Bhatti G, Vijayvergiya R, Singh P, Mastana S, Tewari R, Bhatti J. Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians. ACTA ACUST UNITED AC 2018. [DOI: 10.1159/000494508] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/06/2022]
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Shu S, Bai Y, Wang G, Xiao X, Fan Z, Zhang J, Zhao C, Zhao Y, Xia C, Zhang H. Differentially expressed serum proteins associated with calcium regulation and hypocalcemia in dairy cows. ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES 2016; 30:893-901. [PMID: 27809461 PMCID: PMC5411855 DOI: 10.5713/ajas.16.0615] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 09/22/2016] [Accepted: 11/02/2016] [Indexed: 01/08/2023]
Abstract
Objective Hypocalcemia is an important metabolic disease of dairy cows during the transition period, although the effect of hypocalcemia on biological function in dairy cows remains unknown. Methods In this study, proteomic, mass spectrum, bioinformatics and western blotting were employed to identify differentially expressed proteins related to serum Ca concentration. Serum samples from dairy cows were collected at three time points: 3rd days before calving (day −3), the day of calving (day 0), and 3rd days after calving (day +3). According to the Ca concentration on day 0, a total of 27 dairy cows were assigned to one of three groups (clinical, subclinical, and healthy). Samples collected on day −3 were used for discovery of differentially expressed proteins, which were separated and identified via proteomic analysis and mass spectrometry. Bioinformatics analysis was performed to determine the function of the identified proteins (gene ontology and pathway analysis). The differentially expressed proteins were verified by western blot analysis. Results There were 57 differential spots separated and eight different proteins were identified. Vitamin D-binding protein precursor (group-specific component, GC), alpha-2-macroglobulin (A2M) protein, and apolipoprotein A-IV were related to hypocalcemia by bioinformatics analysis. Due to its specific expression (up-regulated in clinical hypocalcemia and down-regulated in subclinical hypocalcemia), A2M was selected for validation. The results were consistent with those of proteomic analysis. Conclusion A2M was as an early detection index for distinguishing clinical and subclinical hypocalcemia. The possible pathogenesis of clinical hypocalcemia caused by GC and apolipoprotein A-IV was speculated. The down-regulated expression of GC was a probable cause of the decrease in calcium concentration.
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Affiliation(s)
- Shi Shu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Yunlong Bai
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Gang Wang
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Xinhuan Xiao
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Ziling Fan
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Jiang Zhang
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Chang Zhao
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Yang Zhao
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Cheng Xia
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
| | - Hongyou Zhang
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
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Chen ML, Zhao H, Liao N, Xie ZF. Association Between Paraoxonase 2 Ser311Cys Polymorphism and Coronary Heart Disease Risk: A Meta-Analysis. Med Sci Monit 2016; 22:3196-201. [PMID: 27609416 PMCID: PMC5027859 DOI: 10.12659/msm.896601] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background The relationship between coronary heart disease (CHD) and the paraoxonase 2 (PON2) Ser311Cys polymorphism has received much attention. We conducted a meta-analysis on the results from published case-control studies examining this relation. Material/Methods A literature search was performed using PubMed and ISI Web of Knowledge databases until October 2015. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using Stata version 11.0 software. Data were pooled using the random-effects model. Results Nine studies were eligible for statistical analysis and included a total of 5278 participants. The results did not support an association between the Ser311Cys polymorphism and CHD in the overall populations (Asians, Caucasians, and a Hispanic mixed population) under dominant (OR 1.07; 95% CI 0.91–1.28; Pz=0.413), recessive (OR 1.19; 95% CI 0.72–1.95; Pz=0.500), homozygote (OR 1.20; 95% CI 0.71–2.03; Pz=0.489), and allelic comparison (OR 1.08; 95% CI 0.91–1.28; Pz=0.390) models. However, in subgroup analysis according to ethnicity, we found that the Ser311Cys polymorphism was associated with CHD risk in Caucasians under recessive (OR 2.08; 95% CI 1.30–3.34; Pz=0.002) and homozygote (OR 2.16; 95% CI 1.33–3.50; Pz=0.002) models. Subgroup analysis indicated no significant association of this polymorphism with CHD in either Asian or Hispanic populations. Conclusions The PON2 Ser311Cys polymorphism is associated with CHD risk in Caucasians, but there is no association between this polymorphism and CHD in Asians or Hispanic populations.
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Affiliation(s)
- Min-Li Chen
- Department of Geriatrics and Gerontology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Hua Zhao
- Department of Geriatrics and Gerontology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Ning Liao
- Department of Geriatrics and Gerontology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China (mainland)
| | - Zheng-Fu Xie
- Department of Geriatrics and Gerontology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China (mainland)
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Rahman MFA, Hashad IM, Abou-Aisha K, Abdel-Maksoud SM, Gad MZ. Addressing the link between paraoxonase-1 gene variants and the incidence of early onset myocardial infarction. Arch Med Sci 2015; 11:513-20. [PMID: 26170843 PMCID: PMC4495147 DOI: 10.5114/aoms.2015.52353] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Revised: 03/29/2014] [Accepted: 04/19/2014] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was to investigate the association between PON1 Q192R polymorphism, PON1 phenotypes and the incidence of early-onset acute myocardial infarction (AMI) in Egyptians. MATERIAL AND METHODS The study subjects consisted of 102 AMI patients and 72 age-matched healthy controls. Genotyping and enzyme activities were determined using PCR-RFLP and kinetic spectrophotometric assays, respectively. RESULTS The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02%, RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%). Allele frequencies were also significantly different between patients (Q = 62.75%, R = 37.25%) and controls (Q = 79.17%, R = 20.83%). The genotypes QR and RR showed higher risk for AMI compared to the homozygous QQ (odds ratio (OR) = 3.231, p < 0.001). The average PON/ARE ratio in MI patients (1.187 ±0.1) did not differ significantly from controls (1.118 ±0.26). However, it showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (p = 0.0002) and controls (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (p < 0.0001). CONCLUSIONS PON1 192R allele represents an independent risk factor for early-onset AMI in Egyptians, and PON1 Q192R polymorphism modulates the paraoxonase phenotype.
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Affiliation(s)
- Mohamed F Abdel Rahman
- Clinical Biochemistry Unit, Faculty of Pharmacy and Biotechnology, German University, Cairo, Egypt
| | - Ingy M Hashad
- Clinical Biochemistry Unit, Faculty of Pharmacy and Biotechnology, German University, Cairo, Egypt
| | - Khaled Abou-Aisha
- Clinical Biochemistry Unit, Faculty of Pharmacy and Biotechnology, German University, Cairo, Egypt
| | - Sahar M Abdel-Maksoud
- Clinical Biochemistry Unit, Faculty of Pharmacy and Biotechnology, German University, Cairo, Egypt
| | - Mohamed Z Gad
- Clinical Biochemistry Unit, Faculty of Pharmacy and Biotechnology, German University, Cairo, Egypt
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Exploring the role of paraoxonases in the pathogenesis of coronary artery disease: a systematic review. Int J Mol Sci 2014; 15:20997-1010. [PMID: 25405733 PMCID: PMC4264208 DOI: 10.3390/ijms151120997] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2014] [Accepted: 11/10/2014] [Indexed: 12/26/2022] Open
Abstract
Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size <100 patients, non-human studies, editorials and systematic reviews without restrictions on the country of origin. With these criteria, we identified thirty-five prospective studies published between 1986 and 2014 with a total of 28,164 participants. The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies.
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Deshpande CS, Singhal RS, Mukherjee MS. Association of Paraoxonase1 Gene Q192R Polymorphism and Apolipoprotein B in Asian Indian Women with Coronary Artery Disease Risk. Genet Test Mol Biomarkers 2013; 17:140-6. [DOI: 10.1089/gtmb.2012.0193] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Affiliation(s)
- Chetana S. Deshpande
- Food Engineering and Technology Department, Institute of Chemical Technology, Mumbai, India
| | - Rekha S. Singhal
- Food Engineering and Technology Department, Institute of Chemical Technology, Mumbai, India
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Eom SY, Kim YS, Lee CJ, Lee CH, Kim YD, Kim H. Effects of intronic and exonic polymorphisms of paraoxonase 1 (PON1) gene on serum PON1 activity in a Korean population. J Korean Med Sci 2011; 26:720-5. [PMID: 21655055 PMCID: PMC3102863 DOI: 10.3346/jkms.2011.26.6.720] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2010] [Accepted: 03/24/2011] [Indexed: 01/08/2023] Open
Abstract
Paraoxonase 1 (PON1) hydrolyzes a number of toxic organophosphorous compounds and reduces lipid peroxide accumulation, and PON1 genetic polymorphisms in the coding region modulate serum PON1 activity. In this study, we investigated the association between 3 polymorphisms of PON1 located in intron 5 (17899insdelTT and 17974CT) and exon 6 (192QR) and serum PON1 activity. The genetic polymorphisms and serum activity of PON1 were analyzed in 153 healthy Koreans by using a direct sequencing assay and spectrophotometric method, respectively. A significant linkage disequilibrium (LD) was observed between all tested single nucleotide polymorphisms, with the strongest LD observed between 17899insdelTT and 192QR (D' = 0.984). The 17899insdelTT, 17974CT and 192QR genetic polymorphisms were associated with significant differences in serum paraoxonase activity. In multiple regression analyses, smoking, triglyceride level, high-density lipoprotein (HDL) level, and the 17899insdelTT and 192QR genetic polymorphisms were significant determinants of serum paraoxonase activity, while age, smoking, triglyceride level, HDL level, and the 192QR genetic polymorphism were significant determinants of serum arylesterase activity. These results suggest that although the 192QR genetic polymorphism in the coding region of PON1 is primarily associated with serum PON1 activity, the intronic polymorphisms are also involved in serum PON1 activity, and this association may be mediated by LD.
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Affiliation(s)
- Sang-Yong Eom
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Yun-Sik Kim
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Chung-Jong Lee
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Chul-Ho Lee
- Environmental Epidemiology Division, Environmental Health Research Department, National Institute of Environmental Research, Incheon, Korea
| | - Yong-Dae Kim
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Heon Kim
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
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Fujihara J, Yasuda T, Kawai Y, Morikawa N, Arakawa K, Koda Y, Soejima M, Kimura-Kataoka K, Takeshita H. First survey of the three gene polymorphisms (PON1 Q192R, eNOS E298D and eNOS C-786T) potentially associated with coronary artery spasm in African populations and comparison with worldwide data. Cell Biochem Funct 2011; 29:156-63. [DOI: 10.1002/cbf.1721] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2010] [Revised: 12/09/2010] [Accepted: 12/13/2010] [Indexed: 01/08/2023]
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Duygu F, Tekin Koruk S, Aksoy N. Serum paraoxonase and arylesterase activities in various forms of hepatitis B virus infection. J Clin Lab Anal 2011; 25:311-6. [PMID: 21919063 PMCID: PMC6647572 DOI: 10.1002/jcla.20473] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2010] [Accepted: 04/21/2011] [Indexed: 01/09/2023] Open
Abstract
The aim of this study was to determine and evaluate the activity of paraoxonase and arylesterase enzymes in various clinical forms of hepatitis B infection and to investigate the correlation between these parameters and chronic disease course/fibrosis. Overall, 40 patients diagnosed as hepatitis B carriers (CIHBV), 40 chronic active hepatitis B (CAHBV) patients, and 40 healthy adults (control group) between 18 and 65 years of age were enrolled the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Their activities were significantly lower in patients with CAHBV compared with CIHBV patients or with control group patients (P<0.001). There was a negative correlation between alanine aminotransferase levels and the activity of paraoxonase and arylesterase (r = -0.38, P = 0.001 and r = -0.28, P = 0.002, respectively). A statistically significant negative correlation was found between arylesterase activity in the sera of CAHBV patients and HBV DNA levels (ρ = -0.33, P = 0.03). On the contrary, no correlation was found between paraoxonase levels and HBV DNA levels (P>0.05). The histology activity index of CAHBV patients did not correlate with paraoxonase and arylesterase activities (P>0.05). In light of these findings, it may be assumed that during the progression of an inactive hepatitis B carrier to being actively infected, reduced paraoxonase and arylesterase activities may be observed.
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Affiliation(s)
- Fazilet Duygu
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey
| | - Suda Tekin Koruk
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey
| | - Nurten Aksoy
- Department of Biochemistry, Faculty of Medicine, Harran University, Sanliurfa, Turkey
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Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: a meta-analysis based on 88 case-control studies. Atherosclerosis 2010; 214:377-85. [PMID: 21146823 DOI: 10.1016/j.atherosclerosis.2010.11.028] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2010] [Revised: 11/12/2010] [Accepted: 11/12/2010] [Indexed: 01/10/2023]
Abstract
OBJECTIVE The human paraoxonase (PON) is calcium dependent HDL associated ester hydrolase which has attracted considerable attention as a candidate gene for coronary heart disease based on its enzyme function as a key factor in lipoprotein catabolism pathways. Many studies have examined the association between polymorphisms in the PON gene and risk of coronary heart disease (CHD), but the results have been inconsistent. METHODS We conducted a meta-analysis of 88 studies on 4 PON polymorphisms [Q192R, L55M, and T(-107)C in the PON1 and the S311C in the PON2] published before August 2010, including a total of 24,702 CHD cases and 38,232 controls. We also systematically explored potential sources of heterogeneity. RESULT In a combined analysis, the summary per-allele odds ratio for CHD of the 192R was 1.11 (95% CI: 1.05-1.17). However, when the analyses were restricted to 10 larger studies (n>500 cases), the summary per-allele odds ratio was 0.96 (95% CI: 0.90-1.02). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the 55M, (-107)T, and 311C variant showed no significant overall association with CHD, yielding a per-allele odds ratio of 0.94 (95% CI: 0.88-1.00), 1.02 (95% CI: 0.91-1.15) and 1.02 (95% CI: 0.90-1.16) respectively. CONCLUSIONS This meta-analysis suggested an overall weak association between the R192 polymorphism and CHD risk.
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Erdem FH, Karatay S, Yildirim K, Kiziltunc A. Evaluation of serum paraoxonase and arylesterase activities in ankylosing spondylitis patients. Clinics (Sao Paulo) 2010; 65:175-9. [PMID: 20186301 PMCID: PMC2827704 DOI: 10.1590/s1807-59322010000200009] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2009] [Accepted: 11/24/2009] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES The aim of this study was to investigate the activities of serum paraoxonase and arylesterase in patients with ankylosing spondylitis with respect to those of healthy controls, to assess whether these enzyme levels are related to disease activity and functional capacity. METHODS The study included 32 patients with ankylosing spondylitis whose diagnoses were made according to the modified New York criteria as well as 25 healthy controls matched for age and sex. The Bath Ankylosing Spondylitis Disease Activity Index and the Bath Ankylosing Spondylitis Functional Index were applied to the ankylosing spondylitis patients. As laboratory parameters, the erythrocyte sedimentation rate and serum C-reactive protein level were measured in patients and control subjects. Paraoxonase and arylesterase enzyme activities were measured using appropriate methods. RESULTS No statistically significant differences (p>0.05) were found between the ankylosing spondylitis patients and controls in terms of serum paraoxonase or arylesterase levels. Furthermore, there was no correlation between clinical and laboratory parameters in patients with ankylosing spondylitis. CONCLUSION Serum paraoxonase and arylesterase levels in ankylosing spondylitis patients may not differ from those of healthy controls, and there is no significant correlation between antioxidant parameters and the Bath Ankylosing Spondylitis Disease Activity Index or Bath Ankylosing Spondylitis Functional Index scores in ankylosing spondylitis patients. Further research is needed to provide deeper understanding of this disease.
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Abstract
The Change of Ghrelin Levels in Intestinal Parasitic InfectionsThe aim of this work was to examine the relationship between active (acylated ghrelin) and inactive (desacylated ghrelin) ghrelin in the serum and other serum parameters in intestinal parasitic infections and healthy controls. Conventional microscopic methods (saline and iodine solutions, trichrome stain) were used to identify intestinal parasites in stool samples of 29 subjects attending Firat University Hospital. Serum parameters were assessed in a single measurement of serum from 29 parasite subjects, and in 18 healthy controls. Serum acylated ghrelin and desacylated ghrelin levels were measured using a commercial radioimmunoassay (RIA) kit. Paraoxonase and arylesterase were measured by using a spectrophotometer at 405 nm and 270 nm, respectively. Serum concentrations of acylated ghrelin and desacylated ghrelin were more markedly decreased in helminth bearing patients than the control group. Glucose, cholesterol and triglyceride levels were higher in intestinal parasitic infections than in controls. Furthermore, there were no correlations between ghrelin levels and BMI. These results indicate that low ghrelin and PON1/AE level may be important for appetite monitoring in intestinal parasitic infections.
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The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease. Clin Biochem 2009; 43:553-8. [PMID: 20026099 DOI: 10.1016/j.clinbiochem.2009.12.015] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2009] [Revised: 12/10/2009] [Accepted: 12/11/2009] [Indexed: 11/21/2022]
Abstract
OBJECTIVE We tested the association between PON1 polymorphism, PON1 activity, oxidative susceptibility of LDL and coronary artery disease in Egyptians. METHODS PON1 polymorphism, serum PON1 activity, lipoprotein oxidation susceptibility and lipid profile were measured. RESULTS Levels of HDL and paraoxonase activity were significantly decreased in CAD patients compared to control group, and in patients with three vessels compared to those of single or two vessels disease. High-activity allele (R) has a more atherogenic lipid profile than for the low activity allele (Q). PON1 RR genotype has nine fold risks to develop CAD in Egyptians while those with PON1 QR genotype have four fold risks. CONCLUSION The PON1 activity is lower in subject with CAD and there is a significant relationship between activity of PON1 and the severity of coronary atherosclerosis. Also, we provide evidence of a significant association between R allele of the PON1 polymorphism and the development of coronary artery disease.
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Kim NS, Kang BK, Cha MH, Oh SM, Ko MM, Bang OS. Association between PON1 5'-regulatory region polymorphisms, PON1 activity and ischemic stroke. Clin Biochem 2009; 42:857-63. [PMID: 19233151 DOI: 10.1016/j.clinbiochem.2009.02.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2008] [Revised: 02/04/2009] [Accepted: 02/05/2009] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Paraoxonase I (PON1) was known as a risk factor for cerebrovascular diseases. This study assessed the association of single nucleotide polymorphisms (SNPs) in the PON1 5'-regulatory region with ischemic stroke and serum PON1 activity. DESIGN AND METHODS Study subjects consisted of 418 healthy controls and 86 ischemic stroke patients with small vessel occlusion. SNPs were identified by DNA sequencing and a primer extension-based method. RESULTS Among 10 identified SNPs, only -1434GG genotype was observed with a lower frequency in patients on borderline statistical significance (OR(95% CI), 0.297(0.083-1.060), p=0.0615). However, haplotype analysis in a dominant model revealed that ht2 was observed with a significantly lower frequency in patients (OR(95% CI), 0.390(0.153-0.991), p=0.0477). Both C(-1434)G mutation and ht2 distribution were associated with serum PON1 activity. CONCLUSION Our results suggest that haplotypes observed in the PON1 5'-regulatory region should be considered as risk factors for ischemic stroke.
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Affiliation(s)
- No Soo Kim
- Department of Medical Research, Korea Institute of Oriental Medicine, 461-24 Jeonmin-dong, Yuseong-gu, Daejeon, 305-811, Republic of Korea
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Ginsberg G, Neafsey P, Hattis D, Guyton KZ, Johns DO, Sonawane B. Genetic polymorphism in paraoxonase 1 (PON1): Population distribution of PON1 activity. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2009; 12:473-507. [PMID: 20183530 DOI: 10.1080/10937400903158409] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Paraoxonase-1 (PON1) is a serum esterase that hydrolyzes the activated oxon form of several organophosphates. The central role of PON1 in detoxification of organophosphate (OP) pesticides was demonstrated in knockout mouse studies, suggesting that human variability in PON1 needs to be considered in health risk assessments involving exposure to these pesticides. The current analysis focused on two genetic loci in which polymorphisms demonstrated to affect PON1 activity. Detailed kinetic studies and population studies found that the *192Q (wild type) allele is more active toward some substrates (such as sarin, soman, and diazoxon) and less active toward others (such as paraoxon or chlorpyrifos) relative to the variant *192R allele. Another allele that affects activity is *55M; PON1 enzyme quantity, rather than specific activity or substrate preference, is altered. The *192R variant occurs commonly with a frequency of 25-64% across the populations analyzed. The *55M allele is less common, occurring in 5-40% of individuals depending upon the ethnic group studied. These activity and allele frequency data were incorporated into Monte Carlo simulations in which the frequency of both variant alleles was simultaneously modeled in Caucasian, African American, and Japanese populations. The resulting Monte Carlo activity distributions were bimodal for the substrate paraoxon with approximately fourfold differences between low- and high-activity modal medians. Differences in activity between total population median and 1st percentile were five- to sixfold. When sarin metabolic variability was simulated, the population distributions were unimodal. However, there was an even greater degree of interindividual variability (median to 1st percentile difference >20-fold). These results show that the combined effects of two PON1 allelic variants yielded a population distribution that is associated with a considerable degree of interindividual variability in enzyme activity. This indicates that assessments involving PON1 substrates need to evaluate polymorphism-related variability in enzyme activity to display the distribution of internal doses and adverse responses. This may best be achieved via physiologically based pharmacokinetic (PBPK) models that input PON1 activity distributions, such as those generated in this analysis, to simulate the range of oxon internal doses possible across the population.
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Affiliation(s)
- Gary Ginsberg
- Connecticut Department of Public Health, Hartford, 06134, USA.
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Shin BS, Oh SY, Kim YS, Kim KW. The paraoxonase gene polymorphism in stroke patients and lipid profile. Acta Neurol Scand 2008; 117:237-43. [PMID: 17854416 DOI: 10.1111/j.1600-0404.2007.00929.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES The paraoxonase (PON) gene can reduce the risk of developing atherosclerosis. We investigated the associations between PON polymorphisms and ischemic stroke. We also investigated the associations between PON polymorphisms and lipid profile in stroke patients. METHODS A total of 350 patients with ischemic stroke and 242 control subjects in Korean population were genotyped for the PON1M55 L, PON1Q192R, PON2A148 G and PON2S311C polymorphisms using melting point analysis with LightCycler real-time polymerase chain reaction (PCR) technology. RESULTS There were no significant differences in genotype and allele distribution of the PON polymorphisms between the ischemic stroke patients and control subjects. The concentration of total homocysteine was significantly different in the PON1M55 L polymorphism (P = 0.047), and the apolipoprotein (Apo)B concentration was significantly different in the PON1Q192R polymorphism (P = 0.02) in stroke patients. The concentrations of low-density lipoprotein (LDL) cholesterol and ApoB were significantly different between the PON2A148 G (P = 0.011, P = 0.000, respectively) and PON2S311C polymorphisms (P = 0.046, P = 0.003, respectively) in stroke patients. CONCLUSIONS This study did not provide association between PON gene polymorphisms and ischemic stroke. However, it confirmed that the PON1L55 L allele is associated with plasma concentration of total homocysteine and that the PON2G148 G and PON2S311S allele is associated with plasma concentrations of LDL cholesterol and ApoB.
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Affiliation(s)
- B-S Shin
- Department of Neurology, Chonbuk National University Hospital and Medical School, Keumamdong, Jeonju, Chonbuk, Republic of Korea
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Schulpis KH, Barzeliotou A, Papadakis M, Rodolakis A, Antsaklis A, Papassotiriou I, Vlachos GD. Maternal chronic hepatitis B virus is implicated with low neonatal paraoxonase/arylesterase activities. Clin Biochem 2007; 41:282-7. [PMID: 18035058 DOI: 10.1016/j.clinbiochem.2007.10.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2007] [Revised: 10/04/2007] [Accepted: 10/24/2007] [Indexed: 01/29/2023]
Abstract
BACKGROUND Paraoxonase/arylesterase activities are closely implicated with liver function and antiatherogenetic process. AIM To evaluate whether maternal chronic hepatitis B virus, disease (HBV) affect serum neonatal paraoxonase/arylesterase activities. PATIENTS AND METHODS 28 pregnant women with HBV and 28 healthy pregnant women (controls) in the delivery room and their newborns (cord blood) underwent laboratory examinations. Serological virus tests and liver function tests and paraoxonase (PON 1) activities were measured with the Siemens Advia 1650 Clinical Chemistry System, while total antioxidant capacity (TAC) levels and paraoxonase-arylesterase (PON-aryl) activities were measured spectrophotometrically. RESULTS Serological HBV tests and HBV DNA showed chronic HBV (precore mutant G1896A) in the diseased mothers whereas anti-HBc and anti-HBe were detected in their neonates. Liver function parameters were found normal in controls and both groups of newborns. Moderately increased transaminase levels were measured in HBV mothers, whereas TAC levels were decreased in hepatic mothers and their newborns. Interestingly albumin levels did not differ among the studied groups. PON 1 and PON-aryl activities in the diseased mothers (148+/-14 U/mL/min, 130+/-16 KU/mL/min) and their infants (32+/-6 U/mL/min, 24+/-5 KU/mL/min) were significantly lower as compared to those of control mothers (217+/-16 U/mL/min, 196+/-14 KU/mL/min p<0.001) and their newborns (57+/-6 U/mL/min, 48+/-8 UK mL/min p<0.001). Inverse significant correlations were found between the studied enzyme activities and liver enzymes in all the groups of study except in infants born from HBV mothers and positive with TAC in all the studied groups. CONCLUSIONS Decreased PON 1 and PON-aryl activities were measured in infants born from hepatic mothers probably as a consequence of their low TAC. Infants born from HBV mothers are at risk for developing LDL oxidation perinatally.
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Kim NS, Kang K, Cha MH, Kang BJ, Moon J, Kang BK, Yu BC, Kim YS, Choi SM, Bang OS. Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans. Biochem Biophys Res Commun 2007; 364:157-62. [PMID: 17936248 DOI: 10.1016/j.bbrc.2007.09.119] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2007] [Accepted: 09/27/2007] [Indexed: 10/22/2022]
Abstract
Paraoxonase-1 (PON1) is an enzyme associated with HDL in blood and it is considered as an anti-oxidant factor due to its capability to prevent lipid oxidation. In vivo mouse studies also have shown that PON1 is one of the genetic risk factors contributing to atherosclerosis. In this study, we evaluated the serum PON1 activities of sex-age matched Korean healthy control and ischemic stroke patients, and investigated the association of PON1 activity with other metabolic parameters. Statistical analyses revealed that PON1 activity and HDL_cholesterol (HDL_C) in stroke patients were significantly decreased when compared with those of healthy control. Additionally, PON1 activity was negatively correlated with age, whereas it was positively correlated with HDL_C in a stroke group. Overall, the results of this study indicated that decreased serum PON1 activity should be considered as a risk factor for ischemic stroke in Koreans.
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Affiliation(s)
- No Soo Kim
- Department of Medical Research, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea
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21
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Karban A, Hartman C, Eliakim R, Waterman M, Nesher S, Barnett-Griness O, Shamir R. Paraoxonase (PON)1 192R allele carriage is associated with reduced risk of inflammatory bowel disease. Dig Dis Sci 2007; 52:2707-15. [PMID: 17436100 DOI: 10.1007/s10620-006-9700-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2006] [Accepted: 11/26/2006] [Indexed: 01/30/2023]
Abstract
The paraoxonase (PON) genes family maps to chromosome 7q21-q22, within a loci that also showed evidence of susceptibility genes for both Crohn's disease (CD) and ulcerative colitis (UC). In this case-control study we investigated the possible relationship between PON1 and PON2 polymorphisms and the risk of inflammatory bowel disease (IBD). PON1 192Q/R, PON1 55L/M, and PON2 311S/C polymorphisms were investigated by RFLP analysis in DNA samples from 224 patients with CD, 58 patients with UC, and 311 healthy controls. The PON1 192R allele was significantly less common among IBD Ashkenazi patients (allelic OR = 0.61, P = 0.004, 95% CI = 0.44-0.85). In agreement with the individual SNP analysis, Ashkenazi IBD patients had a higher frequency of haplotype PON1 192Q/PON1 55L/PON2 311S (26.3% vs 17.3%; P=0.003) and a lower frequency of haplotype PON1 192R/PON1 55L/PON2 311S (18.9% vs 27.7%; P=0.008). Our results suggest that in this Ashkenazi Jewish population, carriage of PON1 R192 allele may confer protection against the development of IBD.
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Affiliation(s)
- Amir Karban
- Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel
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22
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Robitaille J, Pérusse L, Bouchard C, Vohl MC. Genes, fat intake, and cardiovascular disease risk factors in the Quebec Family Study. Obesity (Silver Spring) 2007; 15:2336-47. [PMID: 17890503 DOI: 10.1038/oby.2007.277] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE The aim of this study was to assess gene-diet interaction effects on cardiovascular disease (CVD) risk factors (waist circumference, plasma triacylglycerol, high-density lipoprotein-cholesterol and fasting glucose concentrations, and diastolic and systolic blood pressure) in the Quebec Family Study cohort. DESIGN Sixty-four polymorphisms from 45 candidate genes were studied in 645 subjects. Dietary fat intake was obtained from a 3-day weighted food record. RESULTS We observed 18 significant interactions at a p value <or= 0.01. Among them, the Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma, alone or in interaction with fat intake, significantly modulated waist circumference (p = 0.0005 for both effects). Additionally, the apolipoprotein E genotype in interaction with fat intake was significantly associated with diastolic and systolic blood pressure (p = 0.01 and p = 0.001, respectively). The ghrelin Leu72Met polymorphism also interacted with dietary fat in its relation to waist circumference and triacylglycerol concentrations (p = 0.0004 and p = 0.005). DISCUSSION These results suggest that several alleles at candidate genes interact with dietary fat intake to modulate well-known CVD risk factors. The identification of gene-diet interaction effects is likely to provide useful information concerning the etiology of CVD.
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Affiliation(s)
- Julie Robitaille
- Lipid Research Center, CHUQ-CHUL, 2705 Laurier Boulevard, TR-93, Ste-Foy, Quebec, Canada G1V 4G2
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Sepahvand F, Rahimi-Moghaddam P, Shafiei M, Ghaffari SM, Rostam-Shirazi M, Mahmoudian M. Frequency of paraoxonase 192/55 polymorphism in an Iranian population. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2007; 70:1125-9. [PMID: 17558807 DOI: 10.1080/15287390701252725] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
Paraoxonase (PON1) is a serum enzyme that plays an important role in prevention of atherosclerosis and also protects against organophosphate-induced neurotoxicity. PON1 displays a high variability in human populations. In this study, PON1-192 and -55 polymorphisms and correlation to serum PON1 activity were investigated in 132 healthy Iranian individuals from Isfahan province. The genotype frequencies for PON1-192 were approximately 48% (QQ), 42.% (QR), and 10% (RR) and for PON1-55 17% (MM), 48% (ML), and 35% (LL). Thus, the frequencies of alleles R and L were 0.31 and 0.59, respectively. PON1 activity toward paraoxon was markedly affected in both polymorphic populations in the following order QQ < QR < RR genotype for PON1-192 and MM < ML < LL genotype for PON1-55. Neither polymorphism significantly affected PON1 activity toward phenylacetate. The RR/LL individuals had the highest PON1 activity and QQ/MM individuals the least. The QR/ML haplotype was the most frequent seen in Iranians, and the RR/MM and QR/MM haplotypes were absent in this population. In conclusion, the frequencies of PON1-192 and -55 polymorphisms in this Iranian population were different from those seen in other Asian populations from Japan and China but similar to those for European Caucasians.
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Affiliation(s)
- Farideh Sepahvand
- Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran
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24
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Lee CH, Kamijima M, Kim H, Shibata E, Ueyama J, Suzuki T, Takagi K, Saito I, Gotoh M, Hibi H, Naito H, Nakajima T. 8-Hydroxydeoxyguanosine levels in human leukocyte and urine according to exposure to organophosphorus pesticides and paraoxonase 1 genotype. Int Arch Occup Environ Health 2006; 80:217-27. [PMID: 16915393 DOI: 10.1007/s00420-006-0128-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2005] [Accepted: 05/23/2006] [Indexed: 10/24/2022]
Abstract
OBJECTIVE In order to investigate a role of paraoxonase 1 (PON1) polymorphism in organophosphorus (OP)-induced 8-hydroxydeoxyguanosine (8-OHdG) levels, urinary metabolites of OP, PON1 genotypes, and 8-OHdG levels in leukocyte and urine were measured in OP indoor insecticide sprayers and controls in summer and winter. METHODS The study population contained 18 male sprayers and age-matched 18 male controls. Sprayers were primarily exposed to OP insecticides (mainly fenitrothion, dichlorvos, chlorpyrifos, and diazinon), and partially to pyrethroids (mainly permethrin) and carbamates (mainly propoxur). Urinary metabolites of OP were measured by gas chromatography-mass spectrometry. 8-OHdG levels in leukocyte and urine were measured by ELISA kit. PON1 genotype was identified using allele-specific fluorogenic TaqMan probes. RESULTS The mean concentrations of urinary dimethyl phosphate (DMP) and total dialkyl phosphates (DAP) in summer and those of 8-OHdG in summer and winter were significantly higher in OP sprayers than controls. This resulted in a significant positive correlation between 8-OHdG levels and urinary DMP or DAP, suggesting a correlation between OP metabolites and production of oxidative stress. Of PON1 genotypes, incidences of Q/Q, Q/R, and R/R types were 17, 39, and 44% in OP sprayers and controls, respectively. Although PON1 polymorphism did not contribute to the leukocyte and urinary 8-OHdG levels, the urinary OP metabolite concentrations in summer showed a significant decrease as the number Q allele decreased. CONCLUSION These results indicate that an increase in OP metabolites is associated with a high level of oxidative stress in OP sprayers, although the contribution of the PON1 polymorphism to the metabolism of OP is still unclear.
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Affiliation(s)
- Chul-Ho Lee
- Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya, Aichi 466-8550, Japan
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25
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Gln192Arg polymorphism in paraoxonase 1 gene is associated with Alzheimer disease in a Chinese Han ethnic population. Chin Med J (Engl) 2006. [DOI: 10.1097/00029330-200607020-00013] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Kilic SS, Aydin S, Kilic N, Erman F, Aydin S, Celik I. Serum arylesterase and paraoxonase activity in patients with chronic hepatitis. World J Gastroenterol 2006; 11:7351-4. [PMID: 16437641 PMCID: PMC4725136 DOI: 10.3748/wjg.v11.i46.7351] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the relationship between serum paraoxonase (PON1), AST, ALT, GGT, and arylesterase (AE) activity alterations and the degree of liver damage in patients with chronic hepatitis. METHODS We studied 34 chronic hepatitis patients and 32 control subjects, aged between 35 and 65 years, in the Department of Infection and Clinical Microbiology at the Firat University School of Medicine. Blood samples were collected from subjects between 8:00 and 10:00 a.m. following a 12-h fast. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. Phenyl acetate was used as the substrate and formed phenol was measured spectrophotometrically at 270 nm after the addition of a 10-fold diluted serum sample in AE activity measurements. RESULTS The results of this investigation revealed that the levels of AE activity decreased from 132+/-52 to 94+/-36 (29%), baseline PON1 activity from 452+/-112 to 164+/-67 (64%), salt-stimulated PON1 activity from 746+/-394 to 294+/-220 (61%), HDL from 58.4+/-5.1 to 47.2+/-5.6 (20%), triglyceride from 133+/-51.2 to 86+/-34.0 (35%), while a slight increase in the level of LDL (from 163+/-54.1 to 177.3+/-56.0; 9%) and significant increases in the levels of AST (from 29+/-9.3 to 98+/-44), ALP (from 57.2+/-13.1 to 91+/-38.1), ALT (from 27.9+/-3.32 to 89+/-19.1), GGT (from 24.3+/-2.10 to 94+/-48.2), total bilirubin (from 0.74+/-0.02 to 1.36+/-0.06; 84%) and direct bilirubin (from 0.18+/-0.01 to 0.42+/-0.04; 133%) were detected. However, the levels of albumin, total protein, cholesterol, and uric acid were almost the same in chronic hepatitis and the control subjects. CONCLUSION Low PON1 and AE activity may contribute to the increased liver dysfunction in chronic hepatitis patients by reducing the ability of HDL to retard LDL oxidation and might be clinically useful for monitoring the disease of chronic hepatitis.
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Affiliation(s)
- Suleyman Sirri Kilic
- Department of Biochemistry and Clinical Biochemistry, Medical School (Firat Medical Center), Firat University, Elazig 23119, Turkey
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27
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Zhang Y, Zheng F, Du H, Krepinsky JC, Segbo JAG, Zhou X. Detecting the polymorphisms of paraoxonase (PON) cluster in Chinese Han population based on a rapid method. Clin Chim Acta 2005; 365:98-103. [PMID: 16185677 DOI: 10.1016/j.cca.2005.07.034] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2005] [Revised: 07/28/2005] [Accepted: 07/29/2005] [Indexed: 10/25/2022]
Abstract
BACKGROUND An increased risk of coronary heart disease has been shown to be associated with polymorphisms in PON1 gene in different populations. Polymorphisms in PON2 gene have been associated with the level of plasma lipoproteins and glucose and are thought to play a role in atherosclerosis. METHODS To detect PONs polymorphisms more rapidly and reliably, we modified and improved the method established by Motti et al. We redesigned the primer for amplifying the common polymorphism at position 311 of PON2, which produced more reliable and efficient amplification. RESULTS A second common polymorphism at codon 148 was also detected by our new method, as were the 2 polymorphisms in the PON1 gene. The new method allowed identification of 4 polymorphisms (PON1-192, PON1-55, PON2-148 and PON2-311) simultaneously. The PONs genotypes of 82 healthy persons were identified by this method. The allelic frequencies were: PON1-192: Q 46.3%, R 53.7%; PON1-55: L 95.1%, M 4.9%; PON2-148: A 85.4%, G 14.6%; PON2-311: S 77.4%, and C 22.6%, respectively. CONCLUSION This method represents a simple, economical and time-saving technique to simultaneously detect 4 polymorphisms in the PON cluster. It provides a useful application to enable further study of the relationship between PON1 and PON2 and their role in atherosclerosis.
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Affiliation(s)
- Ying Zhang
- Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071, P.R. China
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28
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Li J, Wang X, Huo Y, Niu T, Chen C, Zhu G, Huang Y, Chen D, Xu X. PON1 polymorphism, diabetes mellitus, obesity, and risk of myocardial infarction: Modifying effect of diabetes mellitus and obesity on the association between PON1 polymorphism and myocardial infarction. Genet Med 2005; 7:58-63. [PMID: 15654230 DOI: 10.1097/01.gim.0000151152.78092.ca] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
PURPOSE Previous studies on PON1 gene polymorphism and the risk of coronary atherosclerotic diseases have been inconsistent. This may be in part due to population difference in prevalence of high oxidative stress and its modifying effect on the association. Diabetes and obesity are two major risk factors of myocardial infarction (MI) and associated with high oxidative stress. We investigated the association between PON1 Q192R polymorphism and the risk of myocardial infarction (MI) and in particular, whether the association can be modified by diabetes mellitus (DM) and obesity. METHODS We conducted a case-control study, including 154 MI cases and 154 controls enrolled in Beijing, China. Epidemiological and clinical data and PON1 Q192R genotype were obtained from each subject. RESULTS Without considering the modifying effect of DM and obesity, PON1 Q192R polymorphism was not associated with MI. When simultaneously examining the joint association of this polymorphism, DM, and obesity with MI, as compared to subjects with QQ genotypes and without DM and obesity, subjects with QR/RR genotypes and with either DM or obesity had significantly higher risk of MI (OR = 3.6, 95% CI: 1.5-8.7). CONCLUSION Our data suggest that PON1 Q192R polymorphism was not independently associated with MI but further increased the risk of MI among the subjects with DM, obesity, or both, the conditions associated with high oxidative stress.
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Affiliation(s)
- Jianping Li
- Program for Population Genetics, Harvard School of Public Health, Boston, Massachusetts, USA
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Santos NPCD, Ribeiro-dos-Santos ÂKC, Santos SEB. Frequency of the Q192R and L55M polymorphisms of the human serum paraoxonase gene (PON1) in ten Amazonian Amerindian tribes. Genet Mol Biol 2005. [DOI: 10.1590/s1415-47572005000100006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Miwa Y, Takiuchi S, Kamide K, Yoshii M, Horio T, Tanaka C, Banno M, Miyata T, Sasaguri T, Kawano Y. Identification of gene polymorphism in lipocalin-type prostaglandin D synthase and its association with carotid atherosclerosis in Japanese hypertensive patients. Biochem Biophys Res Commun 2004; 322:428-33. [PMID: 15325247 DOI: 10.1016/j.bbrc.2004.07.143] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2004] [Indexed: 10/26/2022]
Abstract
Recent reports suggested that lipocalin-type prostaglandin D synthase (L-PGDS) is implicated in atherogenesis. In the present study, we investigated the polymorphism of the L-PGDS gene and examined its relationship with the severity of carotid atherosclerosis which is determined as the maximum intima-media thickness in the common carotid artery (C-IMT(max)). We identified 6 single nucleotide polymorphisms (SNPs) of the L-PGDS gene in Japanese. A rare SNP with an amino acid change (1535C>G in exon 4, Leu79Val) and a common SNP (4111 A>C in 3'-untranslated region) were selected for genotyping in 782 Japanese hypertensive subjects. There was no significant difference among genotypes in 1535C>G, however, in 4111 A>C, serum levels of high-density lipoprotein (HDL) cholesterol were significantly higher in subjects with A/A genotype than those with A/C and C/C genotypes. C-IMT(max) was significantly smaller in subjects with A/A genotype than those with A/C and C/C. Logistic regression analysis revealed that the presence of A/A genotype significantly reduced the risk for increased C-IMT(max), even after adjustment for other known risk factors [adjusted odds ratio: 0.71 (95% CI: 0.58-0.88)]. Our results suggested that 4111 A>C polymorphism in the L-PGDS gene contributes to the development of carotid atherosclerosis in Japanese hypertensive patients.
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Affiliation(s)
- Yoshikazu Miwa
- Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Japan.
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31
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Lawlor DA, Day INM, Gaunt TR, Hinks LJ, Briggs PJ, Kiessling M, Timpson N, Smith GD, Ebrahim S. The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis. BMC Genet 2004; 5:17. [PMID: 15214960 PMCID: PMC449704 DOI: 10.1186/1471-2156-5-17] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2004] [Accepted: 06/23/2004] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND There have been inconsistent results from case-control studies assessing the association of the PON1 Q192R polymorphism with coronary heart disease (CHD). Most studies have included predominantly men and the association in women is unclear. Since lipid levels vary between the sexes the antioxidant effect of PON1 and any genes associated with it may also vary by sex. We have examined the association of the PON1 Q192R polymorphism with CHD in a large cohort of British women and combined the results from our cohort study with those from all other published studies. RESULTS The distribution of genotypes was the same among women with CHD and those without disease. The odds ratio (95% confidence interval) of having CHD comparing those with either the QR or RR genotype to those with QQ genotype (dominant model of association) was 1.03 (0.89, 1.21) and the per allele odds ratio was 0.98 (0.95, 1.01). In a meta-analysis of this and 38 other published studies (10,738 cases and 17,068 controls) the pooled odds ratio for the dominant effect was 1.14 (1.08, 1.20) and for the per allele effect was 1.10 (1.06, 1.13). There was evidence of small study bias in the meta-analyses and the dominant effect among those studies with 500 or more cases was 1.05 (0.96, 1.15). Ethnicity and reporting of whether the genotyping was done blind to the participants clinical status also contributed to heterogeneity between studies, but there was no difference in effect between studies with 50% or more women compared to those with fewer women and no difference between studies of healthy populations compared to those at high risk (with diabetes, renal disease of familial hypercholesterolaemia). CONCLUSION There is no robust evidence that the PON1 Q192R polymorphism is associated with CHD risk in Caucasian women or men.
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Affiliation(s)
- Debbie A Lawlor
- Department of Social Medicine, University of Bristol, Bristol, UK
| | - Ian NM Day
- Human Genetics Division, School of Medicine, University of Southampton School of Medicine, Southampton, UK
| | - Tom R Gaunt
- Human Genetics Division, School of Medicine, University of Southampton School of Medicine, Southampton, UK
| | - Lesley J Hinks
- Human Genetics Division, School of Medicine, University of Southampton School of Medicine, Southampton, UK
| | - Patricia J Briggs
- Human Genetics Division, School of Medicine, University of Southampton School of Medicine, Southampton, UK
| | - Matthew Kiessling
- Human Genetics Division, School of Medicine, University of Southampton School of Medicine, Southampton, UK
| | - Nick Timpson
- Department of Social Medicine, University of Bristol, Bristol, UK
| | | | - Shah Ebrahim
- Department of Social Medicine, University of Bristol, Bristol, UK
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Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J. Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies. Lancet 2004; 363:689-95. [PMID: 15001326 DOI: 10.1016/s0140-6736(04)15642-0] [Citation(s) in RCA: 198] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Although there have been suggestions that serum paraoxonase is important in protecting against coronary heart disease (CHD), a large number of studies of genetic determinants of serum paraoxonase have reported apparently conflicting results about their association with CHD. METHODS We conducted a meta-analysis of 43 studies of the Q192R, L55M, and T(-107)C polymorphisms in the paraoxonase PON1 gene and the S311C polymorphism in the PON2 gene (all of which are in moderately strong linkage disequilibrium with one another), involving a total of 11212 CHD cases and 12786 controls. We explored potential sources of heterogeneity. FINDINGS In a combined analysis of all studies, the per-allele relative risk of R192 for CHD was 1.12 (95% CI 1.07-1.16), but in the five largest studies it was only 1.05 (0.98-1.13). Combined analyses of studies of the M55, (-107)T, and C311 variants showed no significant overall associations with CHD, yielding per-allele relative risks of 1.00 (0.95-1.06), 1.02 (0.92-1.14), and 1.04 (0.93-1.17), respectively. INTERPRETATION In contrast to previous suggestions, this meta-analysis shows no significant association of CHD with the L55M or T(-107)C polymorphism in PON1 or with the S311C polymorphism in PON2. The weak overall association between the Q192R polymorphism and CHD is of uncertain relevance, particularly since there was no significant association among the larger studies which should be less prone to selective publication. These findings reinforce the need for much larger and more rigorous investigations of the genetic determinants of complex diseases than is now customary, as well as for regularly updated systematic appraisals of such studies to help improve interpretation and prioritise hypotheses.
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Affiliation(s)
- Jeremy G Wheeler
- Department of Public Health and Primary Care, University of Cambridge, Strangeways Site, Wort's Causeway, Cambridge CB1 8RN, UK
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Robertson KS, Hawe E, Miller GJ, Talmud PJ, Humphries SE. Human paraoxonase gene cluster polymorphisms as predictors of coronary heart disease risk in the prospective Northwick Park Heart Study II. Biochim Biophys Acta Mol Basis Dis 2003; 1639:203-12. [PMID: 14636952 DOI: 10.1016/j.bbadis.2003.09.008] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The anti-atherogenic effect of HDL has been suggested to be partly due to the action of HDL-associated paraoxonase (PON). Three distinct enzymes have been identified, encoded by PON1, PON2 and PON3, clustered on chromosome 7q21-q22. Two cSNPs in PON1 (L55M and Q192R) and one in PON2 (S311C) have been implicated as independent risk factors for coronary heart disease (CHD) in some, but not all, studies. A PON3 SNP (A99A) was identified and the effect of these four PON SNPs on HDL levels and CHD risk was examined in the prospective Northwick Park Heart Study II (NPHSII). Genotype frequencies did not differ between cases and controls but the CHD risk associated with smoking was significantly modified by PON1 L55M genotype. Compared to LL non-smokers, LL smokers had a hazard ratio (HR) of 1.30 (95% CI 0.81-2.06) while M-allele carriers had a HR of 1.76 (1.17-2.67). When genotypes were analysed in combination, men with the genotype PON1 55 LM/MM+PON2 311 CC, had HR of 3.54 (1.81-6.93) compared to PON1 LL+PON2 SS/SC men (interaction P=0.004). These effects were independent of classical risk factors. These data demonstrate the importance of stratifying by environmental factors and the use of multiple SNPs for genetic analysis.
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Affiliation(s)
- Kirsty S Robertson
- Division of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University St., London WC1E 6JF, UK
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Ferré N, Tous M, Paul A, Zamora A, Vendrell JJ, Bardají A, Camps J, Richart C, Joven J. Paraoxonase Gln-Arg(192) and Leu-Met(55) gene polymorphisms and enzyme activity in a population with a low rate of coronary heart disease. Clin Biochem 2002; 35:197-203. [PMID: 12074827 DOI: 10.1016/s0009-9120(02)00295-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVES To assess whether paraoxonase (PON1) polymorphisms at positions 55 and 192 and/or their phenotypic expressions influence the risk of myocardial infarction (MI) in Spanish population. DESIGN AND METHODS Two hundred and fifteen male survivors of a MI and their age-matched controls were included in the study. Lipids, apolipoproteins (apo) A-I and B, PON1 activity on paraoxon and phenylacetate and PON1 polymorphisms were determined. RESULTS Genotype distribution was similar in patients and controls. Enzyme activities were lower in patients, but multiple logistic regression analysis did not show any independent association with a higher risk of MI. CONCLUSION None of the PON1 polymorphisms or their corresponding measured activities are independent risk factors for MI in our population.
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Affiliation(s)
- Natàlia Ferré
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Reus, Spain
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