Context: The -629C→A cholesteryl ester transfer protein (CETP) promoter polymorphism is a determinant of HDL cholesterol (HDL-C). The effect of the closely linked CETP TaqIB polymorphism on HDL-C has been suggested to be modified by obesity and hyperinsulinemia. Objective: Because the CETP-mediated cholesteryl ester transfer out of HDL is stimulated by high triglycerides, we hypothesized that triglycerides modify the effect of the CETP -629C→A promoter polymorphism on HDL-C. Design: In 7083 nondiabetic subjects of the PREVEND population, the -629C→A promoter polymorphism, HDL-C, serum triglycerides, waist circumference, and insulin resistance (HOMA ir) were determined. Serum apolipoprotein A-I was available in 6948 subjects. The TaqIB polymorphism was also assessed. Setting: The study is set in the general community. Results: HDL-C and serum apolipoprotein A-I were on average 0.14 mmol/liter and 0.05 g/liter higher in -629AA (22.9%) compared to -629CC (26.8%) homozygotes (P < 0.001 for both). This genotype effect on HDL-C was on average 0.15 mmol/liter in the lowest triglyceride tertile but only 0.08 mmol/liter in the highest tertile (P < 0.01). Multiple regression analysis showed that HDL-C was determined by the CETP promoter variant (P < 0.001), gender (P < 0.001), triglycerides (P < 0.001), and interactions between triglycerides and genotype (P < 0.05), between triglycerides and gender (P < 0.05), and between genotype and gender (P < 0.05), independently from waist, HOMA ir, alcohol use, age, and use of lipid-lowering drugs. The TaqIB polymorphism also interacted with triglycerides on HDL-C. The -629C→A promoter polymorphism did not interact with obesity and HOMA ir on HDL-C. Conclusions: The HDL-C-raising effect of the CETP -629A allele is diminished with higher triglycerides, which may be explained by a predominant effect of triglyceride-rich lipoproteins over circulating CETP itself on cholesteryl ester transfer out of HDL with rising triglycerides. Copyright,
Journal of Clinical Endocrinology and Metabolism
Department of Biochemistry

Borggreve, S., Hillege, H., Wolffenbuttel, B., de Jong, P., Bakker, S., van der Steege, G., … Dullaart, R. (2005). The effect of cholesteryl ester transfer protein -629C→A promoter polymorphism on high-density lipoprotein cholesterol is dependent on serum triglycerides. Journal of Clinical Endocrinology and Metabolism, 90(7), 4198–4204. doi:10.1210/jc.2005-0182