Polymorphisms of the P-selectin gene and risk of myocardial infarction in men and women in the ECTIM extension study

Background and objective-Studies in animal models and humans implicate cell adhesion molecules in atherogenesis but their role in mediating the risk o f myocardial infarction is unclear. The ECTIM (etude cas-temoin Be l'infarc tus myocarde) extension study was established to determine whether a previo usly implicated polymorphism of the P-selectin gene was associated with myo cardial infarction risk in men and women in Belfast and Glasgow. Patients and study setting-696 cases with a recent myocardial infarction an d 561 age matched controls (both male and female) were recruited into a cas e-control study in MONICA project areas of Belfast and Glasgow. Methods-Demographic and lifestyle information was collected by interview ad ministered questionnaire, and each subject was examined and provided a bloo d sample for DNA extraction. The polymerase chain reaction (PCR) was used t o amplify regions encompassing the P-selectin Thr-->Pro (A/C) polymorphism at position 715. Genotype odds ratios for myocardial infarction were estima ted by logistic regression adjusted for population, age, and sex. Results-There was no significant association between conventional risk fact ors (such as hypercholesterolaemia, increased body mass index, or raised bl ood pressure) and either the rare or the common Pro(715) allele of the P-se lectin gene in controls. Overall, comparing Pro(715)/Pro(715) and Pro(715)/ Thr(715) With Thr(715)/Thr(715), With adjustment for centre, age, and sex, the odds ratio was 0.78 (95% confidence interval 0.60 to 1.00) (p = 0.054), indicating a "protective" effect of the less common Pro(715) allele. There was no significant heterogeneity in odds ratios between men and women eith er in this sample or when combined with the original ECTIM subjects. Conclusions-In a large population based study in two regions of the UK we h ave been able to corroborate the earlier ECTIM findings of a lower frequenc y of the Thr/Pro(715) polymorphism in subjects with myocardial infarction. An apparently "protective effect" of similar magnitude also seems to apply to women.