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The relationship between matrix metalloproteinase 1 gene polymorphism and myocardial infarction in Korean subjects
경북대학교 의과대학 내과학교실1, 계명대학교 의과대학 내과학교실2*김희경1․윤태승2․조호찬2․도윤정1․박근규2․이인규1․신동훈2․김혜순2
The matrix metalloproteinases (MMPs) are a family of enzymes that are important in the degradation of collagen fibers and other matrix proteins. MMP-1 expression, which plays an important role in the degradation of collagen types I, II, and III, is significantly increased in vulnerable atherosclerotic plaques with a thin fibrous cap overlaying a large lipid core, compared with stable atherosclerotic plaques with a thick fibrous cap. We investigated whether the polymorphisms in the gene encoding MMP-1 had merit as predictive factor of myocardial infarction. Analyses of 1G/2G polymorphisms at position -1607 in the promoter region of MMP-1 gene in relation to MI risk were performed. Among patients with ischemic heart disease, subjects carrying the homozygous 2G/2G genotype had a higher risk of myocardial infarction compared with subjects with other genotypes (adjusted OR: 2.930; 95% CI: 1.58?3.27), adjusted for age and gender. Furthermore, when compared with control group, subjects carrying the homozygous 2G/2G genotype had a higher risk of myocardial infarction (adjusted OR: 1.457; 95% CI: 0.701?3.029). These findings suggest that the presence of 2G polymorphism at the MMP1 promoter is associated with the development and progression of myocardial infarction, especially in people who already had an ischemic heart disease. We speculate that more transcriptionally active 2G allele of the MMP-1 promote plaque instability and rupture and precipitate MI in 2G/2G genotype. In conclusion, this study shows that 2G/2G genotype at position -1607 in promoter region of MMP-1 may contribute to role as predictive factor of acute myocardial infarction.
Table 1. Genotype distribution for MMP-1 gene at position -1607 SNPs according to clinical diagnosis
Patients Control P value
(n=562) MI group (n=55) Non-MI group (n=143)
MMP-1 -1607 0.025
1G/1G(%) 50.9 42.7 39.7 0.247
1G/2G(%) 30.9 51.0 47.5 0.035
2G/2G(%) 18.2 6.3 12.8 0.034
Table 2. Percentage of subjects with different MMP-1 genotype in MI and non-MI groups
MMP-1 -1607 MI group Non-MI group Crude OR Adjusted OR1
(%) (n=55) (n=143) [95% CI] [95% CI]
1G/1G+1G/2G 81.8 93.7 1 1
2G/2G 18.2 6.3 3.309 2.930
[1.265-8.657] [1.101-7.799]
Table 3. Percentage of subjects with different MMP-1 genotype in MI and control groups
MMP-1 -1607 MI group Control Crude OR Adjusted OR1
(%) (n=55) (n=562) [95% CI] [95% CI]
1G/1G+1G/2G 81.8 87.2 1 1
2G/2G 18.2 12.8 1.512 1.457
[0.730-3.134] [0.701-3.029]
1Odds ratios and 95% CI were calculated by logistic regression, with 1G/1G and 1G/2G genotype as the reference group, and adjusted for age, gender.
