Association of G-33A polymorphism in the thrombomodulin gene with myocardial infarction in Koreans.
Thrombomodulin (TM), a thrombin receptor expressed on the endothelial surface, is known to play an important role in the anti-thrombogenic system in vivo. In this study, we examined the effects of 3 single-nucleotide polymorphisms (SNPs) in the TM gene (G-33A, C1418T and C1922T) on the development of myocardial infarction (MI) in Koreans. We found that G-33A was a common SNP (the minor allele frequency was 0.09) in Koreans. Eighty-five MI patients who had received coronary angiography were enrolled and were divided into 3 groups according to the number of coronary arteries in which stenosis was found angiographically (1-vessel disease (1VD) to 3-vessel disease (3VD)). The criterion of coronary stenosis was 50% or more stenosis on angiography. In addition, 102 controls (CONT) who had no significant stenosis were employed. The number of AA/GA genotypes of G-33A was found to be significantly greater in the 1VD than in the CONT (p=0.004 by chi2-test) while no significant difference was found between the multivessel disease (2-3VD) and the CONT. Multiple logistic analysis showed that G-33A was an independent risk factor for the 1VD with an odds ratio of 4.63 (95% confidence interval; 1.62-13.3). C1418T and C1922T were both in linkage disequilibrium with G-33A; however, they were not independent risks for either the 1VD or the 2-3VD. A reporter gene assay showed that G-33A had a significant effect on the TM promoter activity. These results indicated that G-33A polymorphism in TM might be a genetic risk factor for myocardial infarction.
Department of Laboratory Medicine, Shimane Medical University, Izumo, Japan.
Hyun-Young
HY
Park
Toru
T
Nabika
Yangsoo
Y
Jang
Hyuck Moon
HM
Kwon
Seung Yun
SY
Cho
Junichi
J
Masuda
D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D018180:Thrombomodulin / Q000235:genetics*
D018180:Thrombomodulin