Abstract 9712: Lack of Association Between Common p.T111I Variant in the Endothelial Lipase Gene and the Risk for Coronary Artery Disease in Familial Hypercholesterolemia: Insights From the Modulation of Phospholipids in the HDL Particles

Abstract

Background: endothelial lipase (EL) is a major determinant of high-density lipoprotein cholesterol (HDL-C) metabolism through the lipolysis of the phospholipids (PL) in the HDL particles (HDL-PL). Several studies indicated that common p.T111I variant in EL gene (LIPG: rs2000813) is negatively associated with the risk of coronary artery disease (CAD) independent of HDL-C levels. However, few data exist regarding the influence of this variant on the content of HDL-PL in terms of the association with CAD, especially in familial hypercholesterolemia (FH) subjects. The aim of our study is to elucidate the clinical impact of common p.T111I variant in the EL gene on the content of HDL-PL, and whether this variant could be useful predictor of the risk of CAD in FH subjects, which always exhibit low HDL-C levels. Methods: The p.T111I variant was genotyped in our heterozygous FH subjects (n=80, male=56, mean age=64±18yr, mean TC=340±64mg/dl). All those subjects' plasma lipoproteins were investigated by ultracentrifugation method. Overall HDL-C level, HDL-PL level, and the existence of CAD were investigated for each group (TT group vs. TI and II group). Results: The minor allele frequency in the combined pools of subjects was 0.25. There was no significant association between this variant with overall HDL-C level (42±14 vs. 43±17mg/dl, p=NS) nor with HDL-PL level (86±24 vs. 88±27mg/dl, p=NS). In addition, multiple logistic regression analysis revealed no association between this variant and CAD (odds ratio 0.96, 95%CI:0.88-1.04, p=NS) although significant associations between several coronary risk factors and CAD were observed (figure). Conclusions: These data suggest that common p.T111I variant in LIPG neither plays a role in determining HDL-C as well as HDL-PL levels nor is a useful predictor of the risk of CAD in genetically determined heterozygous FH subjects.