title: Functional genomics of the human high-density lipoprotein receptor scavenger receptor BI:  an old dog with new tricks.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Division of Endocrinology, Metabolism & Clinical Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Alexandra C
authors: AC
authors: Chadwick
authors: Daisy
authors: D
authors: Sahoo
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005298:Fertility; D006801:Humans; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D009154:Mutation; D015539:Platelet Activation; D020641:Polymorphism, Single Nucleotide; D051122:Scavenger Receptors, Class B / Q000097:blood* / Q000235:genetics
chemical_list: D008055:Lipids; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B
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