Cholesterol efflux genes

Sitosterolemia is a rare inherited disease in which plant-derived sterols (sitosterol) accumulate in the body and lead to premature atherosclerotic plaques. The disease is caused by mutations in either of two ATP-binding cassette (ABC) half-transporters, ABCG5 or ABCG8, but the exact role of these genes in the trafficking of sterols has been unclear. In November 18 early edition of Proceedings of the National Academy of Sciences, Liqing Yu and colleagues at the University of Texas Southwestern Medical Center at Dallas, USA, show that ABCG5 and ABCG8 are the major hepatobiliary transporter of both dietary and endogenously synthesized neutral sterols (PNAS, cgi/doi/10.1073/pnas.252582399, November 18, 2002).

Yu et al. generated mice homozygous for a disrupted Abcg5 and Abcg8 allele (G5G8-/-), which they examined for the absorption and secretion of the major dietary plant and animal sterols. They observed that G5G8-/- mice had a two to threefold increase in the fractional absorption of ...