Haplotype analysis of the matrix metalloproteinase 3 gene and myocardial infarction in a Chinese Han population

Xiaoyang Zhou; Jianfeng Huang; Jianhong Chen; Shaoyong Su; Runsheng Chen; Dongfeng Gu

doi:10.1160/TH04-03-0192

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2004; 92(04): 867-873
DOI: 10.1160/TH04-03-0192

Cell Signalling and Vessel Remodelling

Schattauer GmbH

Haplotype analysis of the matrix metalloproteinase 3 gene and myocardial infarction in a Chinese Han population

The Beijing atherosclerosis study

Xiaoyang Zhou

¹Division of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

²National Human Genome Center at Beijing, Beijing, China

,

Jianfeng Huang

¹Division of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

,

Jianhong Chen

¹Division of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

,

Shaoyong Su

¹Division of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

,

Runsheng Chen

³Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

,

Dongfeng Gu

¹Division of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

²National Human Genome Center at Beijing, Beijing, China

› Institutsangaben

Abstract

Summary

Matrix metalloproteinase (MMP) 3 plays an important role in the pathogenesis of myocardial infarction (MI). Up to now, there has been conflicting data regarding the possible contribution of the MMP3 -1612 5A/6A promoter polymorphism to MI. In this study, we have investigated the possible association of three polymorphisms (-1612 5A/6A, -376C/G, Glu45Lys) in the MMP3 gene with MI in a Chinese Han population. The polymorphisms were analyzed in 509 patients with MI, and in 518 healthy controls. The frequency of the 5A allele was 14% in the healthy controls, which is less than in Western populations (40%-52%). Logistic regression analyses of individual polymorphisms indicated that individuals carrying the -1612 5A allele had an increased risk of MI (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.28 to 2.40), as did those carrying the -376 G allele (OR 1.78, 95% CI 1.33 to 2.38). The three polymorphisms studied were found to be in strong linkage disequilibria. Haplotype analyses showed that the 5A-G-Lys haplotype (-1612 5A, -376G and 45Lys) was independently associated with susceptibility to MI. Taken together, the effect of the MMP3 polymorphisms studied may be attributable to the -1612 5A/6A polymorphism. We conclude that the MMP3 -1612 5A/6A polymorphism is associated with MI in our population, implying that individuals of the 5A allele carriers have an increased risk of suffering MI.

Keywords

Metalloproteinase - myocardial infarction - polymorphism - haplotype

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Referenzen

References
1 Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657-71.
2 Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995; 91: 2844-50.
3 Sukhova GK, Schonbeck U, Rabkin E. et al. Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation 1999; 99: 2503-9.
4 Galis ZS, Sukhova GK, Lark MW. et al. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994; 94: 2493-503.
5 Henney AM, Wakeley PR, Davies MJ. et al. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc Natl Acad Sci USA 1991; 88: 8154-8.
6 Woessner Jr JF. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 1991; 05: 2145-54.
7 Ye S, Watts GF, Mandalia S. et al. Preliminary report: genetic variation in the human stromelysin promoter is associated with progression of coronary atherosclerosis. Br Heart J 1995; 73: 209-15.
8 Ye S, Eriksson P, Hamsten A. et al. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression. J Biol Chem 1996; 271: 13055-60.
9 Terashima M, Akita H, Kanazawa K. et al. Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction. Circulation 1999; 99: 2717-9.
10 Nojiri T, Morita H, Imai Y. et al. Genetic variations of matrix metalloproteinase-1 and -3 promoter regions and their associations with susceptibility to myocardial infarction in Japanese. Int J Cardiol 2003; 92: 181-6.
11 Yamada Y, Izawa H, Ichihara S. et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 2002; 347: 1916-23.
12 Beyzade S, Zhang S, Wong YK. et al. Influences of matrix metalloproteinase-3 gene variation on extent of coronary atherosclerosis and risk of myocardial infarction. J Am Coll Cardiol 2003; 41: 2130-7.
13 Gu D, Reynolds K, Wu X. et al. and InterASIA Collaborative Group. The International Collaborative Study of Cardiovascular Disease in ASIA. Prevalence, awareness, treatment, and control of hypertension in china. Hypertension 2002; 40: 920-7.
14 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
15 Xie X, Ott J. Testing linkage disequilibrium between a disease gene and marker loci. Am J Hum Genet 1993; 53: 1107.
16 Zapata C, Carollo C, Rodriguez S. Sampling variance and distribution of the D’ measure of overall gametic disequilibrium between multiallelic loci. Ann Hum Genet 2001; 65: 395-406.
17 Zhao JH, Curtis D, Sham PC. Model-free analysis and permutation tests for allelic associations. Hum Hered 2000; 50: 133-9.
18 Schaid DJ, Rowland CM, Tines DE. et al. Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 2002; 70: 425-34.
19 Lake SL, Lyon H, Tantisira K. et al. Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered 2003; 55: 56-65.
20 Rauramaa R, Vaisanen SB, Luong LA. et al. Stromelysin-1 and interleukin-6 gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis. Arterioscler Thromb Vasc Biol 2000; 20: 2657-62.
21 Gnasso A, Motti C, Irace C. et al. Genetic variation in human stromelysin gene promoter and common carotid geometry in healthy male subjects. Arterioscler Thromb Vasc Biol 2000; 20: 1600-5.
22 Ghilardi G, Biondi ML, DeMonti M. et al. Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with carotid artery stenosis. Stroke 2002; 33: 2408-12.
23 Rundek T, Elkind MS, Pittman J. et al. Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study. Stroke 2002; 33: 1420-3.
24 Humphries SE, Luong LA, Talmud PJ. et al. The 5A/6A polymorphism in the promoter of the stromelysin-1 (MMP-3) gene predicts progression of angiographically determined coronary artery disease in men in the LOCAT gemfibrozil study. Lopid Coronary Angiography Trial. Atherosclerosis 1998; 139: 49-56.
25 de Maat MP, Jukema JW, Ye S. et al. Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary atherosclerosis and restenosis. Am J Cardiol 1999; 83: 852-6.
26 Liu PY, Chen JH, Li YH. et al. Synergistic effect of stromelysin-1 (matrix metallo-proteinase-3) promoter 5A/6A polymorphism with smoking on the onset of young acute myocardial infarction. Thromb Haemost 2003; 90: 132-9.
27 Shah PK. Plaque disruption and coronary thrombosis: new insight into pathogenesis and prevention. Clin Cardiol. 1997 20. II-38-44.
28 Libby P, Geng YJ, Aikawa M. et al. Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 1996; 07: 330-5.
29 Johnson GC, Esposito L, Barratt BJ. et al. Haplotype tagging for the identification of common disease genes. Nat Genet 2001; 29: 233-7.
30 Tregouet DA, Barbaux S, Escolano S. et al. Specific haplotypes of the P-selectin gene are associated with myocardial infarction. Hum Mol Genet 2002; 11: 2015-23.
31 Guetta V, Cannon 3rd RO. Cardiovascular effects of estrogen and lipid-lowering therapies in postmenopausal women. Circulation 1996; 93: 1928-37.