Association of CETP and LIPC Gene Polymorphisms with HDL and LDL Sub-fraction Levels in a Group of Indian Subjects: A Cross-Sectional Study

Abstract

There is an increasing interest to understand the molecular basis of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) subfractions and their association with coronary artery disease (CAD). The formation of these subfractions is greatly influenced by hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) enzymes. To identify genetic markers influencing LDL and HDL subfractions and their role in CAD we performed a case-control genetic association study on 117 healthy controls and 119 angiographically verified CAD patients. Biochemical analysis was performed using standard assays. HDL-C and LDL-C subfractions were estimated using precipitation methods. Genotyping of C-514T (rs1800588) in the LIPC gene for HL and I405V (rs5882) in the CETP gene was done using PCR-based restriction enzyme analysis and sequencing. Both the polymorphisms were not associated with CAD. The C-514T was associated with increased HDL3-C levels in controls (P=0.049). The I405V polymorphism was found to be associated with low levels of small dense, LDL (P=0.038). A multiple regression analysis showed that the effects were dependent on gender and triglyceride levels. We conclude that these polymorphisms are not associated with CAD but are important determinants of HDL-C and small dense LDL particles in our population.