Effect of genetic variations in platelet glycoproteins Ibalpha 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 GP1BA and GP6 and assessed the coronary heart disease (CHD) event rate over 5.8 years of follow-up. 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 GP6 13254TC+CC genotypes by 57% and reduced the HR in patients with the GP1BA -5TC+CC plus GP6 13254TT genotypes by 55% (adj interaction P < .001). In postmenopausal women with established CHD, 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.
Bray
Paul F
PF
Jefferson Medical College and the Cardeza Foundation for Hematologic Research, Philadelphia, PA 19107, USA. paul.bray@jefferson.edu
Howard
Timothy D
TD
Vittinghoff
Eric
E
Sane
David C
DC
Herrington
David M
DM
D000368:Aged; D000483:Alleles; D003327:Coronary Disease / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008525:Medroxyprogesterone / Q000494:pharmacology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D017698:Postmenopause / Q000187:drug effects* / Q000502:physiology*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D004967:Estrogens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C094990:adhesion receptor; C098341:platelet membrane glycoprotein VI; D008525:Medroxyprogesterone