Objective: Impaired estrogen action is a risk factor for coronary artery disease (CAD). Associations of CAD with estrogen receptor a (ERa) polymorphisms, which may influence sensitivity to estrogen, have been reported for men; the data concerning women are not conclusive. We investigated the association of common ERa polymorphisms with the severity of CAD and with metabolic and reproductive factors in postmenopausal women undergoing coronary angiography. Methods: ERa polymorphisms at positions c.454-397 TOC (PvuII) and c.454-351 AOG (XbaI) were studied in 157 women (age 45-88 years). The severity of CAD was assessed by the number of arteries with O50% stenosis in the angiography.Results: There was a significant association between the TT, TC, and CC genotypes (PvuII) and the severity of CAD (PZ0.008); similar results were obtained for the XbaI polymorphism (PZ0.021). These associations were independent of other risk factors for CAD. Women homozygous for the C allele had significantly higher triglyceride and insulin levels; they belonged more frequently to the group with a low number of births (n%1; PZ0.014, Fisher's exact). Conclusions: Common ERa polymorphisms may influence the severity of CAD in women undergoing coronary angiography, reflecting lifetime exposure to estrogen. Similar associations have been reported for men with CAD. These polymorphisms should probably be taken into account when associations with estrogenic actions are examined.
European Journal of Endocrinology 156 489-496