Association of Transforming Growth Factor-β1 Gene Polymorphisms With Myocardial Infarction in Patients With Angiographically Proven Coronary Heart Disease

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Abstract
Objective— Transforming growth factor (TGF)-β1 (TGF-β1) is a multifunctional cytokine that exhibits vasculoprotective properties. Production and plasma levels of TGF-β1 are influenced by polymorphisms in the TGF-β1 gene (TGFB1). We investigated whether the −509C/T (rs1800469), 868T/C (rs1982073), 913G/C (rs1800471), and 11929C/T (rs1800472) polymorphisms of TGFB1 are associated with myocardial infarction. Methods and Results— The study population consisted of 3657 patients with myocardial infarction (885 women and 2772 men) and 1211 control individuals (598 women and 613 men) with angiographically normal coronary arteries and without signs or symptoms of myocardial infarction. Polymorphism-related genotypes were determined with TaqMan assays and haplotypes were estimated from the genotype data. The −509C/T polymorphism and −509C/868T/913G/11929C (CTGC) haplotype were associated with myocardial infarction in men, independently from the potentially confounding factors age, arterial hypertension, hypercholesterolemia, cigarette smoking, and diabetes mellitus. Lower risks of myocardial infarction were observed among the carriers of the −509CC genotype (adjusted odds ratio [OR], 0.49; 95% confidence interval [CI], 0.27 to 0.87; P=0.014) and homozygous carriers of the CTGC haplotype (adjusted OR, 0.61; 95% CI, 0.38 to 0.98; P=0.042) than among the noncarriers of this genotype or haplotype. None of the genotypes (P≥0.37) or haplotypes (P≥0.35) was associated with myocardial infarction in women. Conclusions— Positive association findings in this study suggest that TGFB1 is a susceptibility locus for myocardial infarction. We investigated the association of 4 single nucleotide polymorphisms of the TGF-β1 gene with myocardial infarction in a large white population. The results show that one of the polymorphisms (−509C/T) and a specific haplotype (CTGC haplotype) were associated with myocardial infarction in men but not in women.