Genetic variation of estrogen metabolism and the risks of cardiovascular disease.

Genetic variation in estrogen-metabolizing genes and estrogen receptors influences estrogen metabolism and can potentially modify, at least in part, individual responses to hormone replacement therapy (HRT) or cardiovascular disease (CVD) susceptibility. Pharmacogenetics and association studies of estrogen metabolism genes and lipid levels, inflammatory markers, atherosclerosis and myocardial infarction are reviewed. The human estrogen receptor 1 gene is associated with estrogen metabolism and is the most frequently investigated gene. Few association studies between estrogen receptor 2 variants and CVD risk have been conducted. Although several phase I and II catabolism enzymes are responsible for critical steps in estrogen metabolism, genetic studies with these genes are scarce. Data presented here suggest that genetic variants might influence CVD risk and HRT response. However, no firm conclusions about the clinical implications of these markers can be made based on these studies.