Paolo Zanoni, Sumeet A Khetarpal, Daniel B Larach, William F Hancock-Cerutti, John S Millar, Marina Cuchel, Stephanie DerOhannessian, Anatol Kontush, Praveen Surendran, Danish Saleheen, Stella Trompet, J Wouter Jukema, Anton De Craen, Panos Deloukas, Naveed Sattar, Ian Ford, Chris Packard, Abdullah al Shafi Majumder, Dewan S Alam, Emanuele Di Angelantonio, Goncalo Abecasis, Rajiv Chowdhury, Jeanette Erdmann, Børge G Nordestgaard, Sune F Nielsen, Anne Tybjærg-Hansen, Ruth Frikke Schmidt, Kari Kuulasmaa, Dajiang J Liu, Markus Perola, Stefan Blankenberg, Veikko Salomaa, Satu Männistö, Philippe Amouyel, Dominique Arveiler, Jean Ferrieres, Martina Müller-Nurasyid, Marco Ferrario, Frank Kee, Cristen J Willer, Nilesh Samani, Heribert Schunkert, Adam S Butterworth, Joanna M M Howson, Gina M Peloso, Nathan O Stitziel, John Danesh, Sekar Kathiresan, Daniel J Rader
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...
March 11, 2016: Science