Gallstones, formed when the bile becomes supersaturated with cholesterol, is a common digestive disease that affects 12% of American adults. Although older age (being over 40) is a risk factor for gallstones, women of all ages are more likely to develop gallstones than men are. This sex difference stems from the different way the liver metabolizes cholesterol in response to estrogen. Studies in female mice had established the liver’s classical estrogen receptor α (ERα) as playing a critical role in estrogen-induced gallstones. However, the discovery that GPR30, a G-protein-coupled receptor, acts as a novel estrogen receptor has complicated the understanding of gallstone formation.

David Wang, M.D., Ph.D., has received a four-year, $1.8 million National Institutes of Health grant to study the cellular and molecular mechanisms underlying estrogen-induced gallstones in women. Dr. Wang and his colleagues have identified GPR30 as a new gallstone (Lith) gene, Lith13, in mice. They will investigate whether GPR30 enhances susceptibility to gallstone formation that occurs independently of ERα. Findings from the project may lead to new strategies for treating or even preventing this very common liver disease in women worldwide.

Dr. Wang is a professor of medicine and of genetics at Einstein. (1R01DK126369-01)