Genetics
CETP variant rs708272 raises acute coronary syndrome risk and shifts HDL subclass cholesterol content (Lipids 2018)
Original title: CETP and LCAT Gene Polymorphisms Are Associated with High-Density Lipoprotein Subclasses and Acute Coronary Syndrome
This study evaluated whether CETP polymorphisms rs4783961 and rs708272, and LCAT polymorphism rs2292318, are associated with HDL size distribution, cholesterol content of HDL subclasses, and acute coronary syndrome (ACS) susceptibility, genotyping 619 ACS patients and 607 controls, with a subgroup of 100 healthy individuals used for HDL subclass separation by ultracentrifugation and gel electrophoresis. Under a dominant model, the rs708272 G allele was associated with increased ACS risk (OR 1.45, corrected p=0.036), and a specific linkage disequilibrium combination was also associated with ACS risk (OR 1.52, corrected p=0.02). rs708272 G allele carriers had lower cholesterol in the HDL2a and HDL3a subclasses than A allele carriers. LCAT rs2292318 A allele carriers had lower overall HDL-cholesterol and lower cholesterol across all five HDL subclasses than GG genotype carriers.
Original abstract
We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high-density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions. Under a dominant model, the G allele of the rs708272 polymorphism was associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p-value [pCDom ] = 0.036). The linkage disequilibrium analysis showed that one of the eight possible combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentration of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a lower concentration of high-density lipoprotein-cholesterol (HDL-C) in comparison to the GG genotype; the cholesterol associated with the each one of the five HDL subclasses was significantly lower in rs2292318 A than in GG subjects. In summary, this study demonstrates that the rs708272 polymorphism is associated with a heightened risk of developing ACS. In addition, we report the association of the rs708272 and rs2292318 polymorphisms with HDL-C levels and HDL subclasses.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.