Download PDF
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
1   Division of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2   National Human Genome Center at Beijing, Beijing, China
,
Jianfeng Huang
1   Division 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
1   Division 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
1   Division 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
3   Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
,
Dongfeng Gu
1   Division of Population Genetics and Prevention, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2   National Human Genome Center at Beijing, Beijing, China
› Author AffiliationsFinancial support: This work was funded by grants 2002BA711A05, 2002BA711A08 and 2002BA711A10 of The National Tenth Five-Year Plan Key Programs from Ministry of Science and Technology of The People’s Republic of China and H020220030130 Biomedical Project from the Council of Science and Technology, Beijing.
Further Information

Publication History

Received 27 March 2004

Accepted after revision 04 July 2004

Publication Date:
06 December 2017 (online)

    Permissions and Reprints

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
 

  • References

  • 1 Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657-71.
    CrossrefPubMedGoogle Scholar
  • 2 Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995; 91: 2844-50.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 6 Woessner Jr JF. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 1991; 05: 2145-54.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 15 Xie X, Ott J. Testing linkage disequilibrium between a disease gene and marker loci. Am J Hum Genet 1993; 53: 1107.
    PubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 17 Zhao JH, Curtis D, Sham PC. Model-free analysis and permutation tests for allelic associations. Hum Hered 2000; 50: 133-9.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Shah PK. Plaque disruption and coronary thrombosis: new insight into pathogenesis and prevention. Clin Cardiol. 1997 20. II-38-44.
    PubMedGoogle Scholar
  • 28 Libby P, Geng YJ, Aikawa M. et al. Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 1996; 07: 330-5.
    CrossrefPubMedGoogle Scholar
  • 29 Johnson GC, Esposito L, Barratt BJ. et al. Haplotype tagging for the identification of common disease genes. Nat Genet 2001; 29: 233-7.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 31 Guetta V, Cannon 3rd RO. Cardiovascular effects of estrogen and lipid-lowering therapies in postmenopausal women. Circulation 1996; 93: 1928-37.
    CrossrefPubMedGoogle Scholar