Full resequencing pinpoints the specific CETP promoter and repeat variants most strongly linked to CETP mass and HDL cholesterol (Atherosclerosis 2003)

The cholesteryl ester transfer protein (CETP) gene has been implicated in the variation of HDL levels but most studies have focused on only one or a few genetic variations. In order to properly understand the role of CETP in determining phenotype, it is necessary to examine the entire gene and all its common polymorphisms. The coding regions, adjacent introns, and proximal 5' and 3' regions were resequenced from an ethnically diverse population. Novel and previously known polymorphisms were then characterized and associations with HDL and CETP mass levels determined. The polymorphism most highly associated with CETP was 629 bp upstream of the transcription start site while the polymorphism most highly associated with HDL was a VNTR 1946 bp upstream of the transcription start site. Genetic variation in the CETP gene is associated with protective HDL levels. The ethnic diversity of some SNPs and complex interplay among them dictate careful analysis of the whole gene prior to conclusions about the role of individual polymorphisms.