Figtree, G: Genetic variants in estrogen signaling pathways

Estrogen has a number of important beneficial effects in the cardiovascular system. We hypothesized that genetic variants in the estrogen receptor alpha (ERalpha) gene may cause variable sensitivity to the hormone and influence an individual s risk of cardiovascular disease, along with other estrogen-sensitive phenotypes. This work explores the role of ERalpha in the mediation of the atheroprotective effects of estrogen and identifies regulatory regions in the ERalpha gene important in cardiovascular tissue. It identifies novel genetic variants in these regions and examines their effect on expression of the receptor in vitro, and their association with estrogen sensitive phenotypes in different study populations. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of cardiovascular as well as other estrogen sensitive diseases contributing to the development and application of newer therapies for these disorders.