The association of HDL cholesterol concentration with the −629C>A CETP promoter polymorphism is not fully explained by its relationship with plasma cholesteryl ester transfer

Abstract

Objective. HDL cholesterol is associated with the −629C>A cholesteryl ester transfer protein (CETP) promoter polymorphism. This relationship may in part be explained via effects on plasma cholesteryl ester transfer (CET), which reflects the activity of CETP in the context of endogenous lipoproteins, but also via CET independent pathways involved in HDL metabolism. In this study, we determined the contributions of the CETP −629 C>A genotype, plasma CETP mass and cholesteryl ester transfer to HDL cholesterol. Material and methods. The −629 C>A CETP gene promoter polymorphism, plasma CETP mass, CET, HDL cholesterol, lipids and apolipoprotein (apo) A‐I were measured in 220 non‐diabetic men without cardiovascular disease. Results. Plasma CETP mass (p<0.001) and CET (p<0.001) were higher, whereas HDL cholesterol (p<0.05) and plasma apo A‐I levels (p<0.05) were lower in CC compared to AA carriers. Univariate regression analysis showed that plasma CET was related to the CETP genotype (p = 0.004), plasma CETP mass (p<0.001) and triglycerides (p<0.001). In a multiple linear regression model, HDL cholesterol was related to CETP genotype (p = 0.04) and plasma triglycerides (p<0.001) without independent contributions of plasma CETP mass and CET (p>0.20 for both). Conclusions. This study suggests that, despite a relationship between a common CETP gene variation and plasma cholesteryl ester transfer, the association between CETP gene and HDL cholesterol appears to be at least in part unexplained by the plasma cholesteryl ester transfer process.

• Cholesteryl ester transfer protein polymorphism
• cholesteryl ester transfer
• cholesteryl ester transfer protein
• HDL cholesterol
• triglycerides

Acknowledgements

This study was supported by The Netherlands Heart Foundation (Grant 2001.005). Dr. G. van der Steege, Genotyping Facility, University Medical Center Groningen, Groningen, The Netherlands, is acknowledged for analysing CETP genotypes.