Association between the low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population

Aim Estrogens regulate several biological processes involved in the pathogenesis of myocardial infarction. Catechol-O-methyltransferase (COMT) is a key enzyme in the degradation of estrogens. There is a functional polymorphism in the COMT gene (Val158Met), affecting the activity of the enzyme. We investigated if the low activity genotype of COMT is associated with an altered risk of myocardial infarction. Methods and results In a prospectively followed hypertensive cohort we identified 174 patients who suffered a myocardial infarction during the study and compared them to 348 controls from the same cohort. The COMT polymorphism and serum levels of sex hormones were analysed. Patients homozygous for the low activity COMT genotype had a decreased risk of myocardial infarction compared to those with the high activity genotype, odds ratio 0.65 (95% CI 0.44-0.97, p = 0.033). The protective effect of the low activity genotype was most evident among older patients (>58 years of age), odds ratio 0.43 (95% CI 0.23-0.79, p = 0.006). Serum levels of estradiol were increased (p = 0.006) in mates with the low activity genotype. Conclusions Our findings suggest that the low activity COMT genotype is protective against myocardial infarction. One may speculate that the altered estrogen status could be involved in this effect. (C) 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology.