Effect of genetic variations in platelet glycoproteins Ibα and VI on the risk for coronary heart disease events in postmenopausal women taking hormone therapy

Millions of women still use postmenopausal hormone therapy (HT). We genotyped 2090 women in Heart and Estrogen/ progestin Replacement Study for functional polymorphisms in GP18A and GP6 and assessed the coronary heart disease (CHID) event rate over 5.8 years of followup. In patients receiving placebo, there was an increased CHD death/myocardial infarction (MI)/unstable angina (UA) event rate in carriers of the GP1BA -5C allele (adjusted [adj] P =.006). HT increased the hazard ratio (HR) of CHD events in patients with the GP1BA -5TT genotype by 16% and reduced the HR in patients with the TC+CC genotypes by 46% (adj interaction P < .001). HT reduced the HR in patients with the GP6 13254TT genotype by 17% but increased the HR in patients with the TC+CC genotypes by 35% (adj interaction P < .001). Furthermore, HT increased the HR of CHD events in patients with the GP1BA -5TT plus GP613254TC+CC genotypes by 57% and reduced the HR in patients with the GP1BA -5TC+CC plus GP613254TT genotypes by 55% (adj interaction P <.001). In postmenopausal women with established CHID, these polymorphisms of platelet genes were predictors of CHD events and significantly modified the effects of HT on CHD risk. It will be important to replicate these findings in other studies.