학술논문
A Polynesian-specific missense CETP variant alters the lipid profile
Document Type
article
Author
Jaye Moors; Mohanraj Krishnan; Nick Sumpter; Riku Takei; Matt Bixley; Murray Cadzow; Tanya J. Major; Amanda Phipps-Green; Ruth Topless; Marilyn Merriman; Malcolm Rutledge; Ben Morgan; Jenna C. Carlson; Jerry Z. Zhang; Emily M. Russell; Guangyun Sun; Hong Cheng; Daniel E. Weeks; Take Naseri; Muagututi’a Sefuiva Reupena; Satupa’itea Viali; John Tuitele; Nicola L. Hawley; Ranjan Deka; Stephen T. McGarvey; Janak de Zoysa; Rinki Murphy; Nicola Dalbeth; Lisa Stamp; Mele Taumoepeau; Frances King; Phillip Wilcox; Nuku Rapana; Sally McCormick; Ryan L. Minster; Tony R. Merriman; Megan Leask
Source
HGG Advances, Vol 4, Iss 3, Pp 100204- (2023)
Subject
Language
English
ISSN
2666-2477
Abstract
Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.