Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease.
- Zanoni, P.
- Khetarpal, S.A.
- Larach, D.B.
- Hancock-Cerutti, W.F.
- Millar, J.S.
- Cuchel, M.
- Derohannessian, S.L.
- Kontush, A.
- Surendran, P.
- Saleheen, D.
- Trompet, S.
- Jukema, J.W.
- de Craen, A.J.
- Deloukas, P.
- Sattar, N.
- Ford, I.
- Packard, C.
- Al Shafi Majumder, A.
- Alam, D.S.
- di Angelantonio, E.
- Abecasis, G.
- Chowdhury, R.
- Erdmann, J.
- Nørdestgaard, B.G.
- Nielsen, S.F.
- Tybjærg-Hansen, A.
- Schmidt, R.F.
- Kuulasmaa, K.
- Liu, D.J.
- Perola, M.
- Blankenberg, S.
- Salomaa, V.
- Männistö, S.
- Amouyel, P.
- Arveiler, D.
- Ferrieres, J.
- Müller-Nurasyid, M.
- Ferrario, M.
- Kee, F.
- Willer, C.J.
- Samani, N.
- Schunkert, H.
- Butterworth, A.S.
- Howson, J.M.M.
- Peloso, G.M.
- Stitziel, N.O.
- Danesh, J.
- Kathiresan, S.
- Rader, D.J.
- CHD Exome Consortium ()
- CARDIoGRAM Exome Consortium ()
- Global Lipids Genetics Consortium ()
DOIAbstract
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 variant impairs posttranslational pr...
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