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Background —Transforming growth factor-β (TGF-β) is an important regulator of vascular remodeling and is involved in the pathogenesis of atherosclerosis. A T→C transition at nucleotide 29 of theTGF-β1 gene results in a Leu→Pro substitution at amino acid 10 of the signal peptide. We have now examined a possible association ofTGF-β1 genotype with myocardial infarction (MI) in a Japanese population.Methods and Results —TGF-β1 genotype was determined in 315 Japanese patients (234 men and 81 women) with MI and 591 control subjects (289 men and 302 women). We found that age, body mass index, and incidence of habitual smoking, hypertension, diabetes mellitus, and hypercholesterolemia did not differ between the 2 groups for either men or women. Multivariable logistic regression analysis, however, demonstrated the frequency of theT allele to be significantly higher in male subjects with MI than in controls (TT +TC versusCC ;P &lt;0.0001, odds ratio 3.5, 95% CI 2.0 to 6.3). In contrast, theT allele was not associated with the prevalence of MI in women. In both male MI patients and controls, the serum concentration of TGF-β1 was significantly higher in individuals with theCC genotype than in subjects with theTT orTC genotype.Conclusions —Findings suggest that theT allele at nucleotide 29 in theTGF-β1 gene is a risk factor for genetic susceptibility to MI, at least in middle-aged Japanese men.

Association of a T29→C Polymorphism of the Transforming Growth Factor-β1 Gene With Genetic Susceptibility to Myocardial Infarction in Japanese