LIPIDS: Edited by Annabelle RodriguezFunctional genomics of the human high-density lipoprotein receptor scavenger receptor BI an old dog with new tricksChadwick, Alexandra C.; Sahoo, DaisyAuthor Information aDepartment of Medicine, Division of Endocrinology, Metabolism & Clinical Nutrition bDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA Correspondence to Daisy Sahoo, H4930 Health Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Tel: +1 414 955 7414; fax: +1 414 456 6570; e-mail: [email protected] Current Opinion in Endocrinology & Diabetes and Obesity: April 2013 - Volume 20 - Issue 2 - p 124-131 doi: 10.1097/MED.0b013e32835ed575 Buy Metrics Abstract Purpose of review The athero-protective role of scavenger receptor BI (SR-BI) is primarily attributed to its ability to selectively transfer cholesteryl esters from high-density lipoproteins (HDLs) to the liver during reverse cholesterol transport (RCT). In this review, we highlight recent findings that reveal the impact of SR-BI on lipid levels and cardiovascular disease in humans. Moreover, additional responsibilities of SR-BI in modulating adrenal and platelet function, as well as female fertility in humans, are discussed. Recent findings Heterozygote carriers of P297S, S112F and T175A-mutant SR-BI receptors were identified in patients with high HDL-cholesterol levels. HDL from P297S-SR-BI carriers was unable to mediate macrophage cholesterol efflux, whereas hepatocytes expressing P297S-SR-BI were unable to mediate the selective uptake of HDL-cholesteryl esters. S112F and T175A-mutant receptors exhibited similar impaired cholesterol transport functions in vitro. Reduced SR-BI function in P297S carriers was also associated with decreased steroidogenesis and altered platelet function. Further, human population studies identified SCARB1 variants associated with female infertility. Summary Identification of SR-BI variants confirms the key role of this receptor in influencing lipid levels and RCT in humans. A deeper understanding of the contributions of SR-BI to steroidogenesis, platelet function and fertility is required in light of exploration of HDL-raising therapies aimed at reducing cardiovascular risk. Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.