Estrogen receptor α and β polymorphisms:: is there an association with bone mineral density, plasma lipids, and response to postmenopausal hormone therapy?

Objective and design: A cross-sectional segregation analysis of polymorphisms in the estrogen receptor (ER) genes (Pvull and Xbal in ER alpha, and Alul in ER beta) with bone mineral density in the lumbar spine and forearm and with lipid profile was performed in 1098 postmenopausal women. Additionally, in a subpopulation of 280 women, who completed 1 year of treatment with estrogen plus progestin, the association between genotypes and the response to treatment in both plasma lipids and bone was investigated. In another untreated subpopulation of 443 women, genotype influence on the prevalence of vertebral fractures and on annual rate of bone loss during a mean follow-up period of 11 years was estimated. Results: Baseline plasma lipids, bone mineral density, annual rate of bone loss and prevalence of spinal fractures were not significantly associated with polymorphisms in the ER alpha gene. The ER beta polymorphism was significantly associated with bone loss from the distal forearm (P=0.04) but not with bone loss from the spine. After 1 year of treatment with hormone therapy there was also a significant association between the ER beta polymorphism and the response in total cholesterol (P=0.02); while the ER alpha gene polymorphisms did not significantly influence the response to hormone therapy. Conclusions: In a large white population of postmenopausal women, ER alpha gene polymorphisms were not associated with bone mineral density or lipid profile at baseline or after hormone therapy. Conversely, the ER beta genotype appeared to segregate with bone loss from the forearm and to modulate the decrease in total cholesterol during hormone therapy.