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Beton O, Arslan S, Acar B, Ozbilum N, Berkan O. Association between MMP-3 and MMP-9 polymorphisms and coronary artery disease. Biomed Rep 2016; 5:709-714. [PMID: 28105338 DOI: 10.3892/br.2016.782] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 10/10/2016] [Indexed: 12/20/2022] Open
Abstract
Matrix metalloproteinase (MMP)-3 and MMP-9 polymorphisms are characterized by plaque stability in coronary arteries. The aim of the current study was to investigate the 5A/6A polymorphism in the MMP-3 gene and C/T polymorphism in the MMP-9 gene in patients with coronary artery disease (CAD). The study population consisted of 400 patients who underwent coronary angiography. There were two groups consisting of 200 consecutive patients with CAD, presenting with stable angina pectoris, and 200 consecutive patients exhibiting normal coronary arteries. Two single nucleotide polymorphisms in the MMP gene, MMP-3 and MMP-9, were detected using a polymerase chain reaction-restriction fragment length polymorphism assay. Mean age, gender distribution, smoking status, presence of diabetes mellitus and hypercholesterolemia were identified to be similar between the groups. One hundred and twenty seven (63.5%) patients had hypertension in the CAD group, whereas only 55 (27.5%) patients had hypertension in the control group (P<0.001). No significant difference in frequency of alleles and genotypes of MMP-9 C→T between the CAD and control groups was identified. The 5A allele frequency of MMP-3 in the CAD group was significantly higher when compared with the control group (P<0.001; odds ratio=2.18). The genotype frequency of MMP-3 5A/5A in the CAD group was significantly higher when compared with the controls (P=0.005). When compared with the homozygous wild-type (6A/6A) genotype of the MMP-3 gene, the cumulative frequency of heterozygote and homozygote genotypes of the MMP-3 gene was significantly higher in the CAD compared with the control group (P<0.001). Thus, the present study demonstrated that the 5A/5A and 6A/5A+5A/5A genotypes of the MMP-3 gene were associated with an increased risk of CAD.
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Affiliation(s)
- Osman Beton
- Department of Cardiology, Heart Center, Cumhuriyet University, Sivas 58140, Turkey
| | - Serdal Arslan
- Department of Medical Biology, Cumhuriyet University, Sivas 58140, Turkey
| | - Burak Acar
- Department of Cardiology, Turkiye Yuksek Ihtisas Research and Training Hospital, Ankara 06100, Turkey
| | - Nil Ozbilum
- Molecular Biology and Genetics, Heart Center, Cumhuriyet University, Sivas 58140, Turkey
| | - Ocal Berkan
- Cardiovascular Surgery, Heart Center, Cumhuriyet University, Sivas 58140, Turkey
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Llerena S, Arias-Loste MT, Puente A, Cabezas J, Crespo J, Fábrega E. Binge drinking: Burden of liver disease and beyond. World J Hepatol 2015; 7:2703-2715. [PMID: 26644814 PMCID: PMC4663390 DOI: 10.4254/wjh.v7.i27.2703] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 10/26/2015] [Accepted: 11/11/2015] [Indexed: 02/06/2023] Open
Abstract
The consumption of alcoholic beverages is harmful to human health. In recent years, consumption patterns of alcoholic beverages have changed in our society, and binge drinking has generalized. It is considered to be a socio-sanitary problem with few known consequences in terms of individual and third-party social impacts (in the form of violence or traffic accidents) and its organic impact (affects the liver and other organs and systems, such as the nervous and cardiovascular systems) and represents an important financial burden due to its increasing economic impact. This review provides a global approach to binge drinking and emphasizes its epidemiological character, the effect of this type of consumption and the possible management of a problem with an increasing tendency in our society.
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Qintao C, Yan L, Changhong D, Xiaoliang G, Xiaochen L. Genetic polymorphism of matrix metalloproteinase-1 and coronary artery disease susceptibility: a case-control study in a Han Chinese population. Genet Test Mol Biomarkers 2015; 18:826-31. [PMID: 25372932 DOI: 10.1089/gtmb.2014.0222] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Coronary artery disease (CAD) receives intensive research due to its high incidence and severe impact on the quality of life. One member of the matrix metalloproteinases (MMPs), MMP-1, has been reported to be associated with CAD. To identify the markers contributing to the genetic susceptibility to CAD, nine single-nucleotide polymorphisms (rs1799750, rs498186, rs475007, rs514921, rs494379, rs996999, rs2071232, rs1938901, and rs2239008) throughout the MMP-1 gene were genotyped using MALDI-TOF within the MassARRAY system, and the allele and genotype distributions were compared between 438 healthy controls and 411 patients with CAD from a Chinese Han population. The analysis revealed a weak association between the rs1799750 (in the promoter region) genotype distribution and CAD (p=0.022). An increased risk of CAD was significantly associated with the 2G allele of rs1799750 (p=0.005, odds ratio=1.329, 95% confidence interval=1.090-1.620, after Bonferroni corrections). Strong linkage disequilibrium was observed in three blocks (D'>0.9). Significantly more C-2G (rs498186-rs1799750) haplotypes (p=0.001 after Bonferroni corrections) were found in CAD subjects. These findings point to a role for the polymorphism in the MMP-1 promoter in CAD among a Han Chinese population and may be informative for future genetic or biological studies on CAD.
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Affiliation(s)
- Cui Qintao
- 1 Department of Cardiothoracic Surgery, First Affiliated Hospital of Xinxiang Medical University , Weihui, People's Republic of China
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Li M, Shi J, Fu L, Wang H, Zhou B, Wu X. Genetic polymorphism of MMP family and coronary disease susceptibility: a meta-analysis. Gene 2011; 495:36-41. [PMID: 22226810 DOI: 10.1016/j.gene.2011.12.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2011] [Revised: 11/29/2011] [Accepted: 12/15/2011] [Indexed: 01/05/2023]
Abstract
The issue that genetic polymorphism of matrix metalloproteinase (MMP) family is in association with coronary disease is controversial. So we did a meta-analysis to clarify it clearly. We made a literature search of PubMed, the Web of Science, and Cochrane Collaboration's database to identify eligible reports. The methodological quality of each included studies was assessed. We calculated the pooled ORs with their 95%CI for each genetic polymorphism in STATA 11 software. Separate analysis was performed to address the consistency of results across the subgroup with different continents. A total of 39 studies were included, with a sample of 42269 individuals. This meta-analysis provided evidence that genetic polymorphism of MMP1-1607 1G/2G, MMP3-Gly45lys, MMP3-376 G/C, MMP3-1171 5A/6A, MMP9-1562 C/T and MMP9-R279Q have a small to medium effect on incidence of coronary disease. There was no evidence that MMP1-519 A/G, MMP1-340 T/C and MMP2-1306 C/T polymorphism could increase risk of coronary disease. Results from subgroup analysis supported a relation between MMP3-1711 5A allele, MMP9-1562 C allele and coronary disease especially in Asian population. The results provide moderate association between the six common genetic polymorphism of matrix metalloproteinase family and coronary disease. However, the challenge for researcher is identifying separate effect on different races.
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Affiliation(s)
- Min Li
- Department of Clinical Epidemiology, The First Hospital of China Medical University, Shenyang, PR China
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Langers AM, Verspaget HW, Hommes DW, Sier CF. Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer. World J Gastrointest Oncol 2011; 3:79-98. [PMID: 21731908 PMCID: PMC3124635 DOI: 10.4251/wjgo.v3.i6.79] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Revised: 05/27/2011] [Accepted: 06/03/2011] [Indexed: 02/05/2023] Open
Abstract
Matrix metalloproteinases (MMPs) are implicated in cancer development and progression and are associated with prognosis. Single-nucleotide polymorphisms (SNPs) of MMPs, most frequently located in the promoter region of the genes, have been shown to influence cancer susceptibility and/or progression. SNPs of MMP-1, -2, -3, -7, -8, -9, -12, -13 and -21 and of the tissue inhibitor of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors. The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.
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Affiliation(s)
- Alexandra Mj Langers
- Alexandra MJ Langers, Hein W Verspaget, Daniel W Hommes, Cornelis FM Sier, Department of Gastroenterology and Hepatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
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Maqbool A, Keswani A, Galloway S, O'Regan DJ, Ball SG, Turner NA, Porter KE. MMP-3 (5A/6A) polymorphism does not influence human smooth muscle cell invasion. J Surg Res 2011; 175:343-9. [PMID: 21601886 DOI: 10.1016/j.jss.2011.03.043] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2011] [Revised: 02/11/2011] [Accepted: 03/17/2011] [Indexed: 11/25/2022]
Abstract
BACKGROUND Stromelysin (MMP-3) is an important regulator of vascular smooth muscle cell (SMC) invasion, a key contributor to saphenous vein (SV) bypass graft failure. The 5A allele of the common -1612 MMP-3 5A/6A promoter polymorphism reportedly confers increased promoter activity, MMP-3 tissue expression, and susceptibility to a number of vascular pathologies. The aim of this study was to determine whether the MMP-3 5A/6A polymorphism directly influences endogenous MMP-3 expression levels and, consequently, cell invasion, in SV-derived SMC cultured from patients with different genotypes. MATERIAL AND METHODS Genotyping of 226 patients revealed -1612 MMP-3 5A/6A genotype frequencies of 20.8% 5A/5A, 52.7% 5A/6A, and 26.5% 6A/6A. Using a standardized, controlled protocol, we investigated cytokine- and growth factor-induced MMP-3 expression (real-time polymerase chain reaction [RT-PCR], ELISA) and SV-SMC invasion (Boyden chamber with Matrigel barrier) using cultured SV-SMC from patients with different MMP-3 genotypes. RESULTS Despite observing a strong correlation between MMP-3 mRNA levels and MMP-3 protein secretion, no significant differences were apparent in MMP-3 expression levels or cell invasion between cells with different MMP-3 5A/6A genotypes. CONCLUSIONS Our data suggest that the MMP-3 5A/6A promoter polymorphism in isolation does not influence levels of MMP-3 secretion or cellular invasion in human SV-SMC.
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Affiliation(s)
- Azhar Maqbool
- Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds, UK
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Haplotypes and 5A/6A polymorphism of the matrix metalloproteinase-3 gene in coronary disease: Case–control study and a meta-analysis. Atherosclerosis 2010; 208:171-6. [DOI: 10.1016/j.atherosclerosis.2009.08.021] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2009] [Revised: 08/03/2009] [Accepted: 08/11/2009] [Indexed: 11/24/2022]
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Grant WB, Boucher BJ. Are Hill's criteria for causality satisfied for vitamin D and periodontal disease? DERMATO-ENDOCRINOLOGY 2010; 2:30-6. [PMID: 21547146 PMCID: PMC3084963 DOI: 10.4161/derm.2.1.12488] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2010] [Revised: 05/22/2010] [Accepted: 05/25/2010] [Indexed: 12/31/2022]
Abstract
There is mounting evidence that periodontal disease (PD) is linked to low serum 25-hydroxyvitamin D [25(OH)D] concentrations in addition to recognized risk factors like diet and smoking. This paper reviews this evidence using Hill's criteria for causality in a biological system. Evidence for strength of association, consistency, cohesion and 'dose-effects' [biological 'gradients'] include strong inverse correlations between serum 25(OH) and PD cross-sectionally and that PD is consistently more prevalent in darker vs. lighter skinned people and increases at higher latitudes with analogy for gingivitis and for disorders associated with PD whose risks also increase with hypovitaminosis D. Evidence for plausibility includes that vitamin D increases calcium absorption and protects bone strength; induces formation of cathelicidin and other defensins that combat bacterial infection; reduces tissue production of destructive matrix metalloproteinases actively associated with PD and that prevalence of PD varies with common vitamin D receptor polymorphisms. Experimental evidence from limited supplementation studies [using calcium and vitamin D] shows that supplementation reduces tooth loss. Thus, existing evidence for hypovitaminosis D as a risk factor for PD to date meets Hill's criteria for causality in a biological system. Further experimental evidence for effectiveness and temporality, preferably from randomized controlled trials of vitamin D supplementation [adjusting for other PD risk factors including diet and smoking to reduce confounding] are necessary to confirm causality. If confirmed, dentists and periodontists could perform a valuable service to their patients by discussing the importance of adequate vitamin D status and how to avoid deficiency.
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Affiliation(s)
- William B Grant
- Sunlight, Nutrition; and Health Research Center (SUNARC); San Francisco, CA USA
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Wei JCC, Lee HS, Chen WC, Shiu LJ, Yang SF, Wong RH. Genetic polymorphisms of the matrix metalloproteinase-3 (MMP-3) and tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) modulate the development of ankylosing spondylitis. Ann Rheum Dis 2009; 68:1781-6. [PMID: 19019896 DOI: 10.1136/ard.2008.099481] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND The aetiology of ankylosing spondylitis (AS) remains unclear. Inflammation progresses to fibrosis and calcification of the spine and sacroiliac joints in AS development. Fibrosis results from excessive accumulations of the extracellular matrix (ECM). ECM turnover depends on the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). OBJECTIVE To evaluate the effects of the MMP-3 -1171 and TIMP-1 372 T>C polymorphisms on the modified risk of AS. METHODS Genotypes of 241 patients with AS and 241 controls were identified by PCR. Disease activity and functional status were assessed by the Bath Ankylosing Spondylitis Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Global (BAS-G) Score. RESULTS MMP-3 6A/6A carriers had a 2.41-fold (95% confidence interval (CI) 1.55 to 3.74) increased risk of AS compared with 6A/5A and 5A/5A carriers. TIMP-1 C alleles had a greater risk of AS, but this was not significant (odds ratio (OR) = 1.28, 95% CI 0.92 to 1.77). Pairwise analysis of the MMP-3/TIMP-1 alleles showed that 6A/C (OR = 3.23, 95% CI 1.50 to 6.95) and 6A/T (OR = 2.55, 95% CI 1.17 to 5.54) had a significantly greater risk of AS than the 5A/T alleles. After adjustment for the effects of age, gender and disease duration, the MMP-3/TIMP-1 5A/T alleles had the lowest BASDAI (p = 0.02), BASFI (p = 0.05) and BAS-G (p = 0.02) among all MMP-3/TIMP-1 alleles. CONCLUSION The findings highlight the importance of the MMP-3 and TIMP-1 genes as crucial elements in AS development.
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Affiliation(s)
- J C-C Wei
- Department of Medicine, Chung Shan Medical University, Taichung, Taiwan
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Seifi M, Fallah S, Firoozrai M. Influence of Genetic Polymorphism in Matrix Metalloproteinase-3 on Extent of Coronary Atherosclerosis and Risk of Coronary Artery Stenosis. Arch Med Res 2009; 40:600-4. [DOI: 10.1016/j.arcmed.2009.08.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2009] [Accepted: 08/07/2009] [Indexed: 11/28/2022]
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Association between matrix metalloproteinase-10 concentration and smoking in individuals without cardiovascular disease. Rev Esp Cardiol 2009; 61:1267-73. [PMID: 19080965 DOI: 10.1016/s1885-5857(09)60054-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
INTRODUCTION AND OBJECTIVES Smoking is an important cardiovascular risk factor whose underlying mechanism is incompletely understood. However, it has been suggested that alterations in the balance between synthesis and degradation of the extracellular matrix (ECM) may play a role. The aim of this study was to determine whether there is an independent association between smoking and the concentration of circulating metalloproteinases (MMPs) in individuals without cardiovascular disease. METHODS Metabolic parameters, the carotid intima-media thickness (IMT), inflammatory markers (fibrinogen, C-reactive protein and interleukin-6), markers of endothelial damage (e.g., von Willebrand factor), and the concentration of MMP-1, -9 and -10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in 400 asymptomatic individuals with cardiovascular risk factors. Subjects were divided into non-smokers (n=195), smokers (n=118) and former smokers (n=87). In addition, global cardiovascular risk was determined from PROCAM and REGICOR scores. RESULTS Both MMP-1 and MMP-10 concentrations were significantly higher in smokers than non-smokers (P< .05 and P< .001, respectively), though there was no difference in the levels of MMP-9, TIMP-1, IMT and other inflammatory parameters. There were positive correlations between the MMP-10 concentration and PROCAM and REGICOR scores (P< .001). Multivariate analysis showed that there was still an association between smoking and the MMP-10 concentration after adjustment for age, sex and other cardiovascular risk factors (P< .001). Multiple regression analysis showed that smoking accounted for 28% of the variability in the MMP-10 concentration. CONCLUSIONS There was an independent association between smoking and the MMP-10 concentration in asymptomatic individuals. This relationship between MMP-10 and the ECM may indicate a mechanism through which this MMP contributes to smoking-related atherosclerosis.
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Asociación de la metaloproteinasa-10 y el tabaquismo en sujetos sin enfermedad cardiovascular. Rev Esp Cardiol 2008. [DOI: 10.1016/s0300-8932(08)75734-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Gao LB, Zhou B, Zhang L, Wei YS, Wang YY, Liang WB, Lv ML, Pan XM, Chen YC, Rao L. R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome. BMC MEDICAL GENETICS 2008; 9:74. [PMID: 18664296 PMCID: PMC2515827 DOI: 10.1186/1471-2350-9-74] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/03/2008] [Accepted: 07/30/2008] [Indexed: 11/30/2022]
Abstract
Background Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR) gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS) is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CA)n repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and direct sequencing. Results There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The Lys allele had a significantly increased risk of ACS compared with the Arg allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted P = 0.006). However, no significant relationship between the number of (CA)n repeats of EGFR intron 1 (both alleles < 20 or any allele ≥ 20) and the risk of ACS was observed (adjusted OR = 0.97, 95% CI: 0.58–1.64, adjusted P = 0.911). Considering these two polymorphisms together, there was no statistically significant difference between the two groups. Conclusion R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.
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Affiliation(s)
- Lin-Bo Gao
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan, PR China.
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Kaplan RC, Smith NL, Zucker S, Heckbert SR, Rice K, Psaty BM. Matrix metalloproteinase-3 (MMP3) and MMP9 genes and risk of myocardial infarction, ischemic stroke, and hemorrhagic stroke. Atherosclerosis 2008; 201:130-7. [PMID: 18342317 DOI: 10.1016/j.atherosclerosis.2008.01.003] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2007] [Revised: 12/28/2007] [Accepted: 01/23/2008] [Indexed: 10/22/2022]
Abstract
OBJECTIVE We assessed the association of genetic variation in MMP3 and MMP9 with risk of myocardial infarction and stroke. METHODS A case-control study was conducted among members of Group Health (GH), a large-integrated health care delivery system. Case subjects with incident non-fatal myocardial infarction (n=854), ischemic stroke (n=367), and hemorrhagic stroke (n=66) were identified and validated. A matched control group was selected from among GH members without myocardial infarction or stroke (n=2696). Haplotype-tagging sets of single-nucleotide polymorphisms (SNPs) in MMP3 and MMP9 were genotyped. RESULTS MMP3 haplotype 2 was associated with reduced risk of myocardial infarction (adjusted odds ratio (OR) per copy=0.80, 95% confidence interval 0.66, 0.98) and increased risk of hemorrhagic stroke (OR=1.69, 95% confidence interval 1.05, 2.75). Results for MMP3 haplotype 2 and ischemic stroke resembled those for myocardial infarction but did not achieve statistical significance (OR=0.85, 95% confidence interval 0.64, 1.12). No individual SNP identified MMP3 haplotype 2, and none of the individual MMP3 SNPs were associated with myocardial infarction or stroke. MMP9 haplotypes or SNPs were not associated with myocardial infarction or stroke. CONCLUSIONS MMP3 haplotype may predict both cardiac events and stroke.
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Affiliation(s)
- Robert C Kaplan
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Belfer Building, Room 1306C, 1300 Morris Park Avenue, Bronx, NY, United States.
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Association of the MMP-3 5A/6A gene polymorphism with multiple sclerosis in patients from Serbia. J Neurol Sci 2007; 267:62-5. [PMID: 17942123 DOI: 10.1016/j.jns.2007.09.037] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2007] [Revised: 09/05/2007] [Accepted: 09/27/2007] [Indexed: 01/17/2023]
Abstract
Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in remodeling of the extracellular matrix. MMPs are suggested to play a role in the influx of inflammatory cells into the CNS, disruption of the blood brain barrier, and to degrade myelin in vitro. In this study, we have investigated the possible association of MMP-3 5A/6A gene polymorphism with MS susceptibility and/or severity in patients from Serbia. A total of 184 MS patients (150 RR, 34 SP) and 236 controls have been studied. Results show that the distribution of MMP-3 5A/6A genotype frequencies between MS patients and controls were not significantly different. In bout onset patients, carriers of MMP-3 6A/6A genotype had significantly higher mean MSSS values compared to the carriers of 5A allele (6.29+/-1.89 vs. 5.29+/-2.62, respectively, ANCOVA, p=0.01 Scheffe post-hoc test). In conclusion, our results indicate association of MMP-3 6A/6A genotype with significantly higher mean MSSS values. Thus, the obtained results suggest that it should be carefully considered during follow up of patients with MS. Further genetic and functional studies are needed to resolve the complex role of MMPs and their tissue inhibitors in MS pathology and/or regeneration.
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Horne BD, Camp NJ, Carlquist JF, Muhlestein JB, Kolek MJ, Nicholas ZP, Anderson JL. Multiple-polymorphism associations of 7 matrix metalloproteinase and tissue inhibitor metalloproteinase genes with myocardial infarction and angiographic coronary artery disease. Am Heart J 2007; 154:751-8. [PMID: 17893005 PMCID: PMC2730201 DOI: 10.1016/j.ahj.2007.06.030] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2006] [Accepted: 06/20/2007] [Indexed: 12/27/2022]
Abstract
BACKGROUND Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes may be associated with myocardial infarction (MI) and coronary artery disease (CAD), but studies of multiple MMP genes and their tissue inhibitors (TIMPs) are scarce. Furthermore, differentiation of predictive ability by end point (MI vs CAD) has not been addressed. This study evaluated the association with MI of SNPs in genes encoding MMPs 1, 2, 3, and 9 and TIMPs 1, 2, and 3. METHODS Genotypes of patients (N = 5148) with MI (n = 1693) and angiographically defined CAD (> or = 1 lesion of > or = 70% stenosis, n = 1967) were compared with MI-free (n = 3455) and non-CAD patients (n = 1122), respectively. Because of linkage disequilibrium, MMP-1 and MMP-3 SNPs (chromosome 11) were combined, as were the 2 MMP-9 SNPs. RESULTS For MI, only MMP-9 group CT/RQ (odds ratio [OR] 1.25, P = .007 vs wild-type CC/RR) had greater MI risk, with TT/QQ having a weak trend (OR 1.43, P = .10). These findings remained (CT/RQ) or were strengthened (TT/QQ) after full adjustment. For CAD, association was found for MMP-1/MMP-3 groups 2G1G/6A6A (OR 1.45, P = .022), 2G1G/6A5A (OR = 1.49, P = .001), 2G1G/5A5A (OR 1.64, P = .003), and 1G1G/5A5A (OR 1.35, P = .035) compared to wild type. CONCLUSIONS Composite MMP-9 genotypes but not other SNPs were associated with MI, whereas MMP-1/MMP-3 genotypes were CAD-associated. The largest MMP/TIMP gene study to date, this study suggests care in selection and definition of clinical phenotypes. Furthermore, this suggests that the evaluated SNPs only approximately account for intragenic variation in these genes and that comprehensive evaluation of all variations in these genes should better elucidate associations with MI and CAD phenotypes.
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Affiliation(s)
- Benjamin D Horne
- Cardiovascular Department, LDS Hospital, Intermountain Medical Center, Salt Lake City, UT 84143, USA.
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Giugliano RP, Braunwald E. The Year in Non–ST-Segment Elevation Acute Coronary Syndrome. J Am Coll Cardiol 2007; 50:1386-95. [PMID: 17903640 DOI: 10.1016/j.jacc.2007.05.044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2007] [Accepted: 05/14/2007] [Indexed: 12/19/2022]
Affiliation(s)
- Robert P Giugliano
- TIMI Study Group, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
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Genetic determination of the prognosis in survivors of acute coronary syndromes. Study design and rationale for a multicenter study. COR ET VASA 2007. [DOI: 10.33678/cor.2007.051] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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