CETP and LCAT Gene Polymorphisms Are Associated with High‐Density Lipoprotein Subclasses and Acute Coronary Syndrome

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 [pC ] = 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.

Association of RS708272 (CETP Gene Variant) with Lipid Profile Parameters and the Risk of Myocardial Infarction in the White Population of Western Siberia

“…This finding underscores the importance of not only population-level studies but also research on subjects with specific phenotypes of the lipid profile in order to determine the contribution of genetic factors to the predisposition to common diseases. These observations are consistent with the results of several studies [6,8,9]. For instance, Gilberto Vargas-Alarcon and coworkers demonstrated an association of allele G with a lowered HDL-C concentration and a higher risk of acute coronary syndrome (odds ratio = 1.45, p = 0.036) [8].…”

“…It should be noted that the presence of allele G in various populations has been linked with changes in the activity of the CETP protein, thus leading to lower HDL-C levels, which can raise the risk of CVDs [6,8,9].…”

“…Allele B1 affects the size of the CETP protein, its function, and the HDL-C level. Allele B2 results in a lower molecular weight CETP and in higher HDL-C concentration and—according to some studies—correlates with a lower risk of ischemic heart disease [8,9,10,11]. Other research indicates sex-specific dependence of the associations of the TaqI B polymorphism as well as dependence on the body mass index (BMI), alcohol consumption, and insulin level [12,13].…”

Gender specific effect of CETP rs708272 polymorphism on lipid and atherogenic index of plasma levels but not on the risk of coronary artery disease

“…[26] Vargas-Alarcon et al revealed that this variant was not only associated with the risk of acute coronary syndrome but also with HDL-C levels and HDL subclasses in Mexican mestizos. [27] However, a prospective population-based study conducted in Caucasians demonstrated that CETP rs708272 was associated with increased levels of HDL-C, but not a decreased risk for CAD. [28] To avoid the poorly statistic efficiency caused by small sample size, several meta-analysis studies were also performed to clarity the associations of CETP rs708272 polymorphism and CAD risk and lipid levels.…”

An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases

“…The effect of LCAT on human atherogenesis is controversial [113,114]. Genetic deficiency of LCAT leads to the accumulation of nascent pre-β HDL in the circulation and development of atherosclerosis and acute coronary syndrome [114,115,116,117,118,119,120,121]. In golden Syrian hamsters, the loss of LCAT activity led to dyslipidemia and atherosclerosis [122].…”