The Association of Matrix Metalloproteinase-3 Gene -1612 5A/6A Polymorphism with Susceptibility to Coronary Artery Stenosis in an Iranian Population
Matrix metalloproteinase-3 (MMP3) is key member
of the MMP family, and is known to be present in coronary
atherosclerotic. Several studies have demonstrated that MMP-3
5A/6A polymorphism modify each transcriptional activity in allele
specific manner. We hypothesized that this polymorphism may play
a role as risk factor for development of coronary stenosis. The aim of
our study was to estimate MMP-3 (5A/6A) gene polymorphism on
interindividual variability in risk for coronary stenosis in an Iranian
population.DNA was extracted from white blood cells and genotypes
were obtained from coronary stenosis cases (n=95) and controls
(n=100) by PCR (polymerase chain reaction) and restriction
fragment length polymorphism techniques. Significant differences
between cases and controls were observed for MMP3 genotype
frequencies (X2=199.305, p< 0.001); the 6A allele was less
frequently seen in the control group, compared to the disease group
(85.79 vs. 78%, 6A/6A+5A/6A vs. 5A/5A, P≤0.001). These data
imply the involvement of -1612 5A/6A polymorphism in coronary
stenosis, and suggest that probably the 6A/6A MMP-3 genotype is a
genetic susceptibility factor for coronary stenosis.
[1] Zucker S, Hymowitz M, Conner C, et al. Measurement of matrix
metalloproteinases and tissue inhibitors of metalloproteinases in blood
and tissues. Clinical and experimental applications. Ann NY Acad Sci
1999; 878:212-27.
[2] P.E. Gottschall, S. Deb. Regulation of matrix metalloproteinase
expressions in astrocytes, Neuroimmunomodulation 3 (1996) 69-75.
[3] Nagase H, Woessner Jr JF. Matrix metalloproteinases. J Biol Chem
1999;274:21492-4
[4] Verstappen J, Von den Hoff JW. Tissue Inhibitors of metalloproteinases
(TIMPs): their biological functions and involvement in oral diseases. J
Dent Res 2006; 85:1074-84.
[5] Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling
and atherogenesis: the good, the bad, and the ugly. Circ Res 2002;
90:251- 62
[6] Shah PK, Galis ZS. Matrix metalloproteinase hypothesis of plaque
rupture: players keep piling up but questions
remain.Circulation2001;104:1878-80.
[7] Ye S. Polymorphism in matrix metalloproteinase gene promoters:
implication in regulation of gene expression and susceptibility of various
diseases. Matrix Biol 2000; 19:623-9.
[8] Gerad-Mizon F, de Groote P, Lamblin N, et al. Prognostic impact of
matrix metalloproteinase gene polymorphism in patients with heart
failure according to the etiology of left ventricular systolic dysfunction.
Eur Heart J 2004; 25:688-93.
[9] Fang S, Jin X,Wang R, et al. Polymorphisms in the MMP1 and MMP3
promoter and non-small cell lung carcinoma in North China.
Carcinogenesis 2005; 26:481-6.
[10] 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.
[11] Woessner JF Jr. Matrix metalloproteinases and their inhibitors in
connective tissue remodeling. FASEB J 1991; 5: 2145-54.
[12] 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.
[13] Beyzade S, Zhang S, Wong YK, et al. Influences of
matrixmetalloproteinase-3 gene variation on extent of coronary
atherosclerosis and risk of myocardial infarction. J Am Coll Cardiol
2003; 41:2130-7.
[14] Liu PY, Li YH, Chan SH, et al. Genotype-phenotype association of
matrix metalloproteinase-3 polymorphism and its synergistic effect with
smoking on the occurrence of acute coronary syndrome. Am J Cardiol
2006; 98:1012-7.
[15] Zhou X, Huang J, Chen J, et al. Haplotype analysis of the matrix
metalloproteinase 3 gene and myocardial infarction in a Chinese Han
population. The Beijing atherosclerosis study. Thromb Haemost 2004;
92:867-73.
[16] Kim JS, Park HY, Kwon JH, et al. The roles of stromelysin-1 and the
gelatinase B gene polymorphism in stable angina. Yonsei Med J 2002;
43:473-81.
[17] Lamblin N, Bauters C, Hermant X, et al. Polymorphisms in the promoter
regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as
determinants of aneurysmal coronary artery disease. J AmColl Cardiol
2002; 40:43-8.
[18] Terashima M, Akita H, Kanazawa K, et al. Stromelysin promoter 5A/6A
polymorphism is associated with acute myocardial infarction.
Circulation 1999; 99: 27179.
[19] 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.
[20] Liu PY, Chen JH, Li YH, Wu HL, Shi GY. 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.
[21] Zhou X, Huang J, Chen J, Su S, Chen R, Gu D. Haplotype analysis of
the matrix metalloproteinase 3 gene and myocardial infarction in a
Chinese Han population. The Beijing atherosclerosis study. Thromb
Haemost 2004; 92:867- 73.
[22] Lamblin N, Bauters C, Hermant X, Lablanche JM, Helbecque N,
Amouyel P. Polymorphisms in the promoter regions of MMP-2, MMP-3,
MMP-9 and MMP-12 genes as determinants of aneurismal coronary
artery disease. J Am Coll Cardiol 2002; 40:43 - 8.
[23] Ye S, Watts GF, Mandalia S, Humphries SE, Henney AM. Genetic
variation in the human stromelysin promoter is associated with
progression of coronary atherosclerosis. Br Heart J 1995; 73 :209- 15.
[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] Hirashiki A, Yamada Y, Murase Y, et al. Association of gene
polymorphisms with coronary artery disease in low- or high-risk subjects
defined by conventional risk factors. J Am Coll Cardiol 2003; 42:1429-
37.
[27] Schwarz A, Haberbosch W, Tillmanns H, Gardemann A. The
stromelysin-1 5A/6A promoter polymorphism is a disease marker for the
extent of coronary heart disease. Dis Markers 2002;18:121-8.
[28] Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for
extracting DNA from human nucleated cells. Nucleic Acids Res 1988;
16:1215.
[29] Boerma M, Forsberg L, Van Zeijl L, et al. A genetic polymorphism in
connexin 37 as a prognostic marker for atherosclerotic plaque
development. J Intern Med 1999; 246:211 - 8.
[30] Hirashiki A, Yamada Y, Murase Y, Suzuki Y, Kataoka H, Morimoto Y,
et al. Association of gene polymorphisms with coronary artery disease in
low- or high-risk subjects defined by conventional risk factors. J Am
Coll Cardiol 2003; 42:1429-37.
[31] Hoppmann P, Koch W, Schomig A, Kastrati A. The 5A/6A
polymorphism of the stromelysin-1 gene and restenosis after
percutaneous coronary interventions. Eur Heart J 2004; 25:335-41
[32] Ye S, Gale CR, Martyn CN. Variation in the matrix metalloproteinase-1
gene and risk of coronary heart disease. Eur Heart J 2003; 24:1668-71.
[33] Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s.
Nature 1993; 362:801-9.
[34] Libby P. Molecular bases of the acute coronary syndromes. Circulation
1995; 91:2844- 50.
[35] Davies MJ. Stability and instability: two faces of coronary
atherosclerosis. The Paul Dudley White Lecture 1995. Circulation 1996;
94:2013-20.
[36] Silence J, Lupu F, Collen D, Lijnen HR. Persistence of atherosclerotic
plaque but reduced aneurysm formation in mice with stromelysin-1
(MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol 2001;
21:1440- 5.
[1] Zucker S, Hymowitz M, Conner C, et al. Measurement of matrix
metalloproteinases and tissue inhibitors of metalloproteinases in blood
and tissues. Clinical and experimental applications. Ann NY Acad Sci
1999; 878:212-27.
[2] P.E. Gottschall, S. Deb. Regulation of matrix metalloproteinase
expressions in astrocytes, Neuroimmunomodulation 3 (1996) 69-75.
[3] Nagase H, Woessner Jr JF. Matrix metalloproteinases. J Biol Chem
1999;274:21492-4
[4] Verstappen J, Von den Hoff JW. Tissue Inhibitors of metalloproteinases
(TIMPs): their biological functions and involvement in oral diseases. J
Dent Res 2006; 85:1074-84.
[5] Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling
and atherogenesis: the good, the bad, and the ugly. Circ Res 2002;
90:251- 62
[6] Shah PK, Galis ZS. Matrix metalloproteinase hypothesis of plaque
rupture: players keep piling up but questions
remain.Circulation2001;104:1878-80.
[7] Ye S. Polymorphism in matrix metalloproteinase gene promoters:
implication in regulation of gene expression and susceptibility of various
diseases. Matrix Biol 2000; 19:623-9.
[8] Gerad-Mizon F, de Groote P, Lamblin N, et al. Prognostic impact of
matrix metalloproteinase gene polymorphism in patients with heart
failure according to the etiology of left ventricular systolic dysfunction.
Eur Heart J 2004; 25:688-93.
[9] Fang S, Jin X,Wang R, et al. Polymorphisms in the MMP1 and MMP3
promoter and non-small cell lung carcinoma in North China.
Carcinogenesis 2005; 26:481-6.
[10] 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.
[11] Woessner JF Jr. Matrix metalloproteinases and their inhibitors in
connective tissue remodeling. FASEB J 1991; 5: 2145-54.
[12] 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.
[13] Beyzade S, Zhang S, Wong YK, et al. Influences of
matrixmetalloproteinase-3 gene variation on extent of coronary
atherosclerosis and risk of myocardial infarction. J Am Coll Cardiol
2003; 41:2130-7.
[14] Liu PY, Li YH, Chan SH, et al. Genotype-phenotype association of
matrix metalloproteinase-3 polymorphism and its synergistic effect with
smoking on the occurrence of acute coronary syndrome. Am J Cardiol
2006; 98:1012-7.
[15] Zhou X, Huang J, Chen J, et al. Haplotype analysis of the matrix
metalloproteinase 3 gene and myocardial infarction in a Chinese Han
population. The Beijing atherosclerosis study. Thromb Haemost 2004;
92:867-73.
[16] Kim JS, Park HY, Kwon JH, et al. The roles of stromelysin-1 and the
gelatinase B gene polymorphism in stable angina. Yonsei Med J 2002;
43:473-81.
[17] Lamblin N, Bauters C, Hermant X, et al. Polymorphisms in the promoter
regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as
determinants of aneurysmal coronary artery disease. J AmColl Cardiol
2002; 40:43-8.
[18] Terashima M, Akita H, Kanazawa K, et al. Stromelysin promoter 5A/6A
polymorphism is associated with acute myocardial infarction.
Circulation 1999; 99: 27179.
[19] 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.
[20] Liu PY, Chen JH, Li YH, Wu HL, Shi GY. 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.
[21] Zhou X, Huang J, Chen J, Su S, Chen R, Gu D. Haplotype analysis of
the matrix metalloproteinase 3 gene and myocardial infarction in a
Chinese Han population. The Beijing atherosclerosis study. Thromb
Haemost 2004; 92:867- 73.
[22] Lamblin N, Bauters C, Hermant X, Lablanche JM, Helbecque N,
Amouyel P. Polymorphisms in the promoter regions of MMP-2, MMP-3,
MMP-9 and MMP-12 genes as determinants of aneurismal coronary
artery disease. J Am Coll Cardiol 2002; 40:43 - 8.
[23] Ye S, Watts GF, Mandalia S, Humphries SE, Henney AM. Genetic
variation in the human stromelysin promoter is associated with
progression of coronary atherosclerosis. Br Heart J 1995; 73 :209- 15.
[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] Hirashiki A, Yamada Y, Murase Y, et al. Association of gene
polymorphisms with coronary artery disease in low- or high-risk subjects
defined by conventional risk factors. J Am Coll Cardiol 2003; 42:1429-
37.
[27] Schwarz A, Haberbosch W, Tillmanns H, Gardemann A. The
stromelysin-1 5A/6A promoter polymorphism is a disease marker for the
extent of coronary heart disease. Dis Markers 2002;18:121-8.
[28] Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for
extracting DNA from human nucleated cells. Nucleic Acids Res 1988;
16:1215.
[29] Boerma M, Forsberg L, Van Zeijl L, et al. A genetic polymorphism in
connexin 37 as a prognostic marker for atherosclerotic plaque
development. J Intern Med 1999; 246:211 - 8.
[30] Hirashiki A, Yamada Y, Murase Y, Suzuki Y, Kataoka H, Morimoto Y,
et al. Association of gene polymorphisms with coronary artery disease in
low- or high-risk subjects defined by conventional risk factors. J Am
Coll Cardiol 2003; 42:1429-37.
[31] Hoppmann P, Koch W, Schomig A, Kastrati A. The 5A/6A
polymorphism of the stromelysin-1 gene and restenosis after
percutaneous coronary interventions. Eur Heart J 2004; 25:335-41
[32] Ye S, Gale CR, Martyn CN. Variation in the matrix metalloproteinase-1
gene and risk of coronary heart disease. Eur Heart J 2003; 24:1668-71.
[33] Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s.
Nature 1993; 362:801-9.
[34] Libby P. Molecular bases of the acute coronary syndromes. Circulation
1995; 91:2844- 50.
[35] Davies MJ. Stability and instability: two faces of coronary
atherosclerosis. The Paul Dudley White Lecture 1995. Circulation 1996;
94:2013-20.
[36] Silence J, Lupu F, Collen D, Lijnen HR. Persistence of atherosclerotic
plaque but reduced aneurysm formation in mice with stromelysin-1
(MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol 2001;
21:1440- 5.
@article{"International Journal of Medical, Medicine and Health Sciences:56495", author = "M. Seifi and S. Fallah and M. Firoozrai", title = "The Association of Matrix Metalloproteinase-3 Gene -1612 5A/6A Polymorphism with Susceptibility to Coronary Artery Stenosis in an Iranian Population", abstract = "Matrix metalloproteinase-3 (MMP3) is key member
of the MMP family, and is known to be present in coronary
atherosclerotic. Several studies have demonstrated that MMP-3
5A/6A polymorphism modify each transcriptional activity in allele
specific manner. We hypothesized that this polymorphism may play
a role as risk factor for development of coronary stenosis. The aim of
our study was to estimate MMP-3 (5A/6A) gene polymorphism on
interindividual variability in risk for coronary stenosis in an Iranian
population.DNA was extracted from white blood cells and genotypes
were obtained from coronary stenosis cases (n=95) and controls
(n=100) by PCR (polymerase chain reaction) and restriction
fragment length polymorphism techniques. Significant differences
between cases and controls were observed for MMP3 genotype
frequencies (X2=199.305, p< 0.001); the 6A allele was less
frequently seen in the control group, compared to the disease group
(85.79 vs. 78%, 6A/6A+5A/6A vs. 5A/5A, P≤0.001). These data
imply the involvement of -1612 5A/6A polymorphism in coronary
stenosis, and suggest that probably the 6A/6A MMP-3 genotype is a
genetic susceptibility factor for coronary stenosis.", keywords = "Coronary artery stenosis, matrixmetalloproteinase-3, polymorphism, polymerase chain reaction.", volume = "3", number = "4", pages = "27-4", }
