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Severity of cardiovascular disease in postmenopausal women: associations with common estrogen receptor polymorphic variants

¹ Endocrine Unit, Evgenidion Hospital and ² Department of Medical Therapeutics, Alexandra Hospital, Athens University School of Medicine, 11528 Athens, Greece and ³ Medical Genetics Unit, Department of Obstetrics and Gynaecology, University of Ioannina, Medical School, 45110 Ioannina, Greece

(Correspondence should be addressed to M Alevizaki who is now at Athens University School of Medicine, 80, Vassilisis Sofias Ave., 11528 Athens, Greece; Email: mani{at}otenet.gr)

Objective: Impaired estrogen action is a risk factor for coronary artery disease (CAD). Associations of CAD with estrogen receptor (ER) 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 ER polymorphisms with the severity of CAD and with metabolic and reproductive factors in postmenopausal women undergoing coronary angiography.

Methods: ER polymorphisms at positions c.454–397 T>C (PvuII) and c.454–351 A>G (XbaI) were studied in 157 women (age 45–88 years). The severity of CAD was assessed by the number of arteries with >50% stenosis in the angiography.

Results: There was a significant association between the TT, TC, and CC genotypes (PvuII) and the severity of CAD (P=0.008); similar results were obtained for the XbaI polymorphism (P=0.021). 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 (n1; P=0.014, Fisher’s exact).

Conclusions: Common ER 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.