Submitted March 28, 2006
Accepted October 11, 2006
Effect of genetic variations in platelet glycoproteins Ib
and VI on the risk for coronary heart disease in postmenopausal women taking hormone therapy
Paul F. Bray*, Timothy D Howard, Eric Vittinghoff, David C Sane, and David M Herrington
Baylor College of Medicine, Houston, TX
Wake Forest University School of Medicine, Winston Salem, NC
Dept of Epidemiology & Biostatistics, University of California at San Francisco, CA
* Corresponding author; email: paul.bray{at}jefferson.edu.
Millions of women still use postmenopausal hormone treatment (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/MI/UA event rate in carriers of the GP1BA -5C allele (adjusted [adj.] P=0.006). 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<0.0001). HT reduced the HR in patients with the GP6 TT genotype by 17%, but increased the HR in patients with the TC+CC genotypes by 35% (adj. interaction P<0.0001). 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 -5 TC+CC plus GP6 13254TT genotypes by 55% (adj. interaction P=0.0002). In postmenopausal women with established CHD, 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.
