Contribution of the TGFB1 Gene to Myocardial Infarction Susceptibility

Abstract

Carriage frequencies of alleles and genotypes of the TGFB1 gene polymorphous loci -509CT (rs1800469), 869TC (rs1982073), 915GC (rs1800471), which affect the level of cytokine TGF-1 production, were analyzed in the patients of Russian ethnic descent with myocardial infarction (MI) (406 cases) and in the control group of the same ethnic descent (198 controls). Significant association with MI was observed in carriage frequencies of the allele TGFB1*-509T (p=0.046, OR =1.45, 95% CI: 1.02-2.06), genotypes TGFB1*869T/T (p=0.0024, OR =1.75, 95% CI: 1.22-2.51), and TGFB1*915G/G (p=0.048, OR=1.76, 95% CI: 1.05-2.97). Linkage disequilibrium analysis for these SNPs has shown that the associations revealed can be considered to be independent. A complex analysis of MI association with combinations of alleles/genotypes of said SNPs indicates their cumulative effect. An analysis of susceptibility to early-onset MI ( 50 years old) revealed a positive association of the allele TGFB1*-509T (p=0.002, OR=2.24, 95% CI: 1.35-3.71) and genotype TGFB1*869T/T (p=0.008, OR=1.93, 95% CI: 1.18-3.15), as well as their additivity. An analysis of susceptibility to recurrent MI revealed an association of the genotype TGFB1*-509T/T (p=0.0078, 0R=2.60, 95% CI: 1.28-5.28). The results obtained indicate the important role of the TGFB1 gene in susceptibility to MI, including early-onset and recurrent MI, in Russians.