TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study

BACKGROUND AND PURPOSE: Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cardiovascular and cerebrovascular complications. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with a central role in inflammation. Little is known of the relation of variations within the gene and risk of cardiovascular and cerebrovascular disease. We therefore investigated 5 polymorphisms in the TGF-beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the risk of myocardial infarction and stroke in a population-based study. METHODS: Participants (N=6456) of the Rotterdam Study were included in the current study. Analyses of the relations of genotypes with the risk of myocardial infarction and stroke were performed according to Cox proportional-hazards methods. All analyses were adjusted for age, sex, conventional cardiovascular risk factors, and medical history. RESULTS: We found no association with the risk of myocardial infarction. A significantly increased risk of stroke was found, associated with the T allele of the -509 C/T polymorphism (relative risk, 1.26; (95% CI, 1.06 to 1.49) and the Pro variant of the codon 10 polymorphism (relative risk, 1.24; 95% CI, 1.04 to 1.48). CONCLUSIONS: No association between the TGF-beta1 polymorphisms and myocardial infarction was observed; however, the -509 C/T and codon 10 Leu/Pro polymorphisms were associated with the risk of stroke.