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

Sequencing 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 ("β" HDLmeta = 0.236 mmol/L [95% CI 0.211; 0.260]) and lower LDL-C ("β" LDLmeta = -0.133 mmol/L [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.