Genetics
CETP variant rs17231506 is one of five genes shaping sex-specific cholesterol efflux capacity independent of HDL-C (Arterioscler Thromb Vasc Biol 2013)
Original title: Genetic determination of plasma cholesterol efflux capacity is gender-specific and independent of HDL-cholesterol levels
Researchers measured whole-plasma cholesterol efflux capacity from cholesterol-loaded human macrophages in 846 individuals (450 men, 396 women) and tested how genetic variants in HDL-related genes affect it. Five single-nucleotide polymorphisms, including CETP c.-1337 C>T (rs17231506) along with variants in ABCA1, APOA1, APOAII, and LIPC, significantly modulated plasma efflux capacity in a sex-dependent manner, independent of circulating HDL-cholesterol, triglyceride, or LDL-cholesterol levels. In women, the APOA1 and LIPC variants were the major contributors to efflux-capacity variability, while in men the ABCA1 and APOAII variants contributed most; together the seven SNPs tested accounted for approximately 6% of total plasma efflux capacity. The authors conclude that genetically determined efflux capacity is a better predictor of macrophage cholesterol removal than plasma HDL-cholesterol levels.
Original abstract
Objective: We investigated the impact of several genetic variants located in genes encoding for proteins involved in biogenesis, maturation, and intravascular remodeling of high density lipoprotein (HDL) particles on plasma efflux capacity.
Approach And Results: The capacity of whole-plasma to mediate cholesterol efflux from cholesterol-loaded human THP-1 macrophages was measured in 846 individuals (450 men and 396 women). We demonstrated that rs17231506 (CETP c.-1337 C>T), rs2230806 (ABCA1 p.R219K), rs1799837 (APOA1 c.-75 G>A), rs5086 (APOAII c.-265 T>C), and rs1800588 (LIPC c.-514 C>T) single nucleotide polymorphisms (SNPs) significantly modulate the capacity of whole-plasma to mediate cholesterol efflux from human macrophages in a sex-dependent manner. Such associations were independent of circulating plasma lipid levels (HDL-cholesterol, triglyceride, low density lipoprotein-cholesterol). In women, we identified the APOA1 c.-75 G>A and the LIPC c.-514 C>T variants as major contributors of interindividual variability of plasma efflux capacity, whereas the ABCA1 p.R219K and the APOAII c.-265 T>C SNPs mostly contribute to total variance of plasma efflux capacity in men. Multiple regression analyses revealed that the 7 SNPs tested accounted together for approximately 6% of total plasma efflux capacity. We demonstrated that genetically determined plasma efflux capacity represents a better predictor of macrophage cholesterol removal, as compared with plasma HDL-cholesterol levels.
Conclusions: Genetic variants located within genes encoding proteins involved in HDL metabolism significantly impact plasma efflux capacity independently of variation in plasma HDL-cholesterol levels.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.