Genetics
Dense genotyping of the CETP gene in over 2,000 people pinpoints a promoter SNP at position -4,502 as likely functional for HDL cholesterol (J Lipid Res 2007)
Original title: High-density genotyping and functional SNP localization in the CETP gene
Although hundreds of genetic analyses of the CETP gene have typically focused on a small number of polymorphisms within a single ethnic group, the extent of DNA beyond the transcribed sequence that may influence CETP expression had not been well defined. To better characterize natural variation modulating CETP and HDL cholesterol levels, researchers performed dense genotyping of CETP and up to 15 kb of flanking sequence on either side in more than 2,000 individuals. This revealed a complex, nonlinear set of linkage disequilibrium bins interspersed across large regions of the gene, and confirmed associations of known functional SNPs with HDL cholesterol while suggesting additional uncharacterized functional SNPs exist. By comparing associations across different ethnic groups, the researchers narrowed the likely functional SNP set, identifying the promoter SNP at position -4,502, the variant most strongly associated with HDL cholesterol, as likely functional because it alters a consensus transcription factor binding site.
Original abstract
The cholesteryl ester transfer protein gene (CETP) has been the subject of hundreds of genetic analyses that typically focus on a small number of polymorphisms within a single ethnic group. Furthermore, the extent of DNA beyond the transcribed sequence from which single nucleotide polymorphisms (SNPs) may influence CETP expression has not been well defined. To better understand the role of natural variation in modulating CETP and high density lipoprotein-cholesterol (HDL-C) levels, dense genotyping of CETP and regions up to 15 kb on either side of the gene was carried out on >2,000 individuals. A complex, nonlinear set of linkage disequilibrium bins was found, with many bins interspersed along the DNA sequence and spread over large regions of the gene. Bins assigned based on large numbers of individuals matched the small subset of SNPs that had been assigned to bins previously with a small number of individuals. Associations of known functional SNPs with HDL-C were found, but there were suggestions that there are additional functional SNPs not characterized previously. Narrowing of the set of likely functional SNPs was accomplished by comparing associations observed in different ethnic groups. The promoter SNP most highly associated with HDL-C that is likely to be functional, position -4,502, alters a consensus transcription factor binding site.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.