GENOTYPE DISTRIBUTION OF ESTROGEN-RECEPTOR POLYMORPHISMS IN MEN AND POSTMENOPAUSAL WOMEN FROM HEALTHY AND CORONARY POPULATIONS AND ITS RELATION TO SERUM-LIPID LEVELS

The cardiovascular protective effects of estrogen are known to be medi ated by its beneficial effects on lipid metabolism and its direct acti ons on the vessel wall. The latter can be mediated by a specific recep tor for estrogen present on smooth muscle cells and endothelial cells. The gene for the receptor (the classic estrogen receptor [ER]) has th ree known polymorphisms, Pvu II, Xba I, and B-variant polymorphisms, w hich are reportedly associated with receptor expression and altered re ceptor function and with some disorders including breast cancer, hyper tension, and spontaneous abortion. However. the significance of geneti c variations of the ER in vascular diseases has not been reported. We have examined the association between coronary artery disease (CAD) an d the three polymorphisms in ER. Genotypes (P1/P2, X1/X2, and B-wild t ype/B-variant type) were determined in 87 men and postmenopausal women with myocardial infarction or angina pectoris whose lesions were conf irmed by coronary angiography, as well as from 94 control individuals from the general population with no coronary heart disease and normal resting EGG. For B-variant polymorphism, all individuals examined had B-wild type, which contrasts with the reported allele frequency for B- variant type (0.1) in the white population. Genotype distributions and allele frequencies of Pvu II or Xba I polymorphisms were not signific antly different between control subjects and patients (P>.05 for Pvu I I or Xba I genotypes; P>.05 for Pvu II or Xba I allele frequencies). W hen the allele frequencies were analyzed separately by sex, there was still no statistically significant difference for both polymorphisms ( P>.05 for men; P>.05 for women). No association was found between the polymorphisms and the angiographic severity of CAD. Total cholesterol, triglyceride, or HDL-cholesterol levels were not significantly differ ent among ER genotypes. These findings suggest that the three polymorp hisms in ER are not associated with the prevalence and severity of CAD and that the polymorphisms are unrelated to the serum lipid levels in control subjects and patients.