Genetics
A highly variable repeat in the CETP promoter forms unusual DNA structures and predicts HDL-C levels (Biochim Biophys Acta 2004)
Original title: Highly polymorphic repeat region in the CETP promoter induces unusual DNA structure
Researchers characterized a highly polymorphic variable-length tandem repeat located 1946 base pairs upstream of the CETP transcription start, finding more than 10 different long alleles varying in repeat structure. The short allele of this repeat was significantly associated with high HDL cholesterol levels in vivo (P<0.0001), an association independent of the nearby -629 polymorphism in men. The variable-length GAAA repeat was also found to stimulate an adjacent GGGGA repeat to form an unusual DNA structure that hinders PCR amplification and sequencing, an effect also demonstrated in vivo through orientation effects and cloning efficiency in E. coli. The authors conclude this repeat region contributes both to CETP gene regulation and to technical challenges in genotyping the CETP promoter.
Original abstract
Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter is associated with HDL cholesterol levels and cardiovascular disease with much of the genetic variation in CETP attributed to the promoter region. In this region, there are several single nucleotide polymorphisms as well as a variable length tandem repeat located 1946 base pairs upstream of the CETP transcription start that is highly polymorphic with respect to both length and sequence. There are more than 10 different long alleles and these vary in their repeat structure. We find that the short allele of this repeat is associated with high HDL cholesterol levels in vivo (P<0.0001). In males, this association is independent of the nearby -629 polymorphism. In addition, the variable length GAAA repeat can stimulate an adjacent GGGGA repeat to form a structure that hinders DNA amplification and sequencing. This structure also has an effect in vivo as shown by orientation effects and cloning efficiency in Escherichia coli.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.