Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L…

• DD
  Doris Duke Charitable Foundation
• A
  Amgen
• BS
  Bristol-Myers Squibb
• EL
  Eli Lilly and Company
• A
  AstraZeneca
• S
  Sanofi
• AP
  Alnylam Pharmaceuticals
• RP
  Regeneron Pharmaceuticals
• NI
  National Institutes of Health

  Award: TL1R000138
• MR
  Medical Research Council

  Awards: MR/K013351/1, MR/L003120/1, MR/N003284/1
• NC
  National Center for Research Resources

  Award: TL1RR024133
• NC
  National Center for Advancing Translational Sciences

  Award: TL1R000138