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Cholesteryl ester transfer protein promoter single‐nucleotide polymorphisms in Sp1‐binding sites affect transcription and are associated with high‐density lipoprotein cholesterol
Author(s) -
Thompson JF,
Lloyd DB,
Lira ME,
Milos PM
Publication year - 2004
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2004.00289.x
Subject(s) - cholesterylester transfer protein , allele , biology , promoter , genetics , cholesterol , high density lipoprotein , polymorphism (computer science) , population , lipoprotein , transcription (linguistics) , microbiology and biotechnology , gene , endocrinology , gene expression , medicine , environmental health , linguistics , philosophy
Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter has been shown to be associated with high‐density lipoprotein cholesterol (HDL‐C) levels and cardiovascular disease. Some of this variation occurs in Sp1/Sp3 binding sites in the proximal promoter. We find that both the known promoter polymorphism at −629 and the previously uncharacterized polymorphism at −38 are associated with HDL‐C levels in vivo and affect transcription in vitro . While the −629 polymorphism is common in all ethnic groups, the −38 polymorphism is found at significant levels (6.4%) only among African Americans. Those homozygous for the less common −38A allele have higher HDL‐C levels than those with the more frequent −38G allele. This association was found in a population of African Americans at risk of cardiovascular disease and then replicated in a different population chosen from among patients with extremes of HDL‐C. When studied in vitro , the most transcriptionally active allele (−629C/−38G) yields 51% more reporter protein than the least active allele (−629A/−38A) in HepG2 cells. These transcriptional effects reflect the projected impact of increased CETP expression on HDL‐C phenotypes seen in vivo .