Abstract 5919: Cholesteryl Ester Transfer Protein Genotype Predicts Anti-atherogenic Lipid Profile and Decreased Risk of Ishemic Heart Disease, Ischemic Cerebrovascular Disease, and Death Not Attributable to HDL Cholesterol Alone
Background: CETP facilitates exchange of cholesteryl esters for triglycerides between HDL and triglyceride-rich lipoproteins. Although this exchange clearly may effect many atherogenic lipoproteins in plasma, any association with risk of ischemic heart disease(IHD) has traditionally been attributed to HDL cholesterol (HDL-C) alone.
Objectives: To determine to what extent a common(allele frequency=0.44), functional genetic variant in CETP, TaqIBG>A(in linkage disquilibrium with −629C>A), predicts:
changes in lipid and lipoprotein profile, including levels of non-fasting triglycerides and remnant cholesterol;
risk of IHD, ischemic cerebro-vascular disease(ICVD), and mortality in the general population.
Methods and Results: We genotyped 10,092 participants in the Copenhagen City Heart Study. Besides a stepwise increase in HDL-C(GG vs. GA and GG vs. AA, ΔHDL=6.8% and 13.5%), TaqIB genotype associated with stepwise decreases in non-fasting triglycerides(GG vs. GA and GG vs. AA, Δ = −3.7% and −5.8%), LDL-C(−1.9% and −3.2%), and remnant cholesterol(−3,7% and −6.1%), all of which are independent predictors of IHD, ICVD, and death. In agreement with this anti-atherogenic profile, we observed stepwise reductions in risk of IHD(GG vs. GA, hazard ratio(95%CI)=0.83(0.75– 0.92) and GG vs. AA, 0.72(0.63– 0.82)), ICVD(0.84(0.71– 0.98) and 0.74(0.60 – 0.92)) and overall death(0.97(0.89 –1.05) and 0.83(0.75– 0.92)) as a function of Taq1B genotype.
Conclusion: In the general population, TaqIBG>A genotype associates with an anti-atherogenic lipid profile, and with corresponding reductions in risk of IHD, ICVD and overall death which cannot be attributed to an increase in HDL-C alone.