A population-specific missense variant rs1597000001 in CETP promotes a favorable lipid profile and reduces CETP activity

Author:

Moors Jaye,Krishnan Mohanraj,Sumpter Nick,Takei Riku,Bixley Matt,Cadzow Murray,Major Tanya J.,Phipps-Green Amanda,Topless Ruth,Merriman Marilyn,Rutledge Malcolm,Morgan Ben,Carlson Jenna C.,Zhang Jerry Z.,Russell Emily M.,Sun Guangyun,Cheng Hong,Weeks Daniel E.,Naseri Take,Sefuiva Reupena Muagututi‘a,Viali Satupa‘itea,Tuitele John,Hawley Nicola L.,Deka Ranjan,McGarvey Stephen T.,de Zoysa Janak,Murphy Rinki,Dalbeth Nicola,Stamp Lisa,Taumoepeau Mele,King Frances,Wilcox Philip,McCormick Sally,Minster Ryan L.,Merriman Tony R.,Leask Megan

Abstract

ABSTRACTSequencing of CETP in Māori and Pacific peoples identified a common (MAF ∼2.4%-5.4%) population-specific missense variant (rs1597000001, CETP:c.530C>T p.Pro177Leu) that associates with higher HDL-C levels ( [95% CI 0.211; 0.260]) and lower LDL-C ( [95% CI -0.209; -0.058]). In a subsample of the study cohort (n = 11), heterozygous carriers of the population-specific variant had lower plasma CETP activity (P = 0.028). Our study identifies a population-specific missense variant in CETP which lowers CETP activity with an effect on HDL-C that is comparable to Mendelian CETP loss-of-function mutations.

Publisher

Cold Spring Harbor Laboratory

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