Genetics
CETP TaqIB predicts heart attack risk and a 2-year later age of onset, but a linked promoter variant does not, Reykjavik Study finds (Atherosclerosis 2001)
Original title: The -629C>A polymorphism in the CETP gene does not explain the association of TaqIB polymorphism with risk and age of myocardial infarction in Icelandic men
This study tested whether the established effect of CETP TaqIB on HDL-cholesterol and myocardial infarction (MI) risk could be explained by the closely linked -629C>A promoter polymorphism, in 388 male non-fatal MI cases and 794 healthy male controls from the 30-year Reykjavik Study. B2B2 homozygotes had 15% higher HDL-cholesterol than B1B1, and -629AA homozygotes had 14% higher HDL-cholesterol than -629CC (both P less than 0.0001). Lower-HDL alleles were more frequent in cases than controls for both TaqIB B1 (0.59 vs 0.53) and -629C (0.52 vs 0.48, P less than 0.05 for both). B1B1 homozygotes had significantly higher MI risk (OR 1.44, 95% CI 1.10-1.87), an effect not seen for CC homozygotes (OR 1.16, 95% CI 0.87-1.54). TaqI B2B2 homozygotes had their first MI 2 years later than other genotypes (59 vs 61, P less than 0.05), an effect not seen for the promoter polymorphism.
Original abstract
The aim of this study was to examine whether the well-established effect of the common TaqIB polymorphism in intron 1 of the gene for cholesterol ester transfer protein (CETP) on high density lipoprotein cholesterol (HDL-C) concentration and increased risk of myocardial infarction (MI), could be explained by the recently identified -629C>A functional polymorphism in the promoter. Non-fatal MI cases (388 male) and a control group of 794 healthy men were recruited from the 30 year long prospective Reykjavik Study. In the healthy men the frequency of the TaqIB B2 allele was 0.47 (95% CI: 0.44-0.50) and there was a strong allelic association with the -629A allele (D=-0.21, P<0.0001), which had a frequency of 0.52 (95% CI: 0.49-0.56). B2B2 homozygotes displayed 15% higher HDL-C levels than subjects homozygous for the B1 allele (P<0.0001). Homozygotes for the -629A allele displayed 14% higher HDL-C concentrations than subjects homozygous for the -629C allele (P<0.0001). The frequencies of the alleles associated with lower HDL-C were significantly higher in cases compared with controls, 0.59 versus 0.53 (TaqIB B1) and 0.52 versus 0.48 (-629 C) respectively (P<0.05 for both). There was a significantly higher risk for MI in B1B1 homozygotes (OR=1.44, 95% CI: 1.10-1.87, P<0.01), compared to the other genotypes combined. This was not observed for the CC homozygotes (OR=1.16, 95% CI: 0.87-1.54). In addition, homozygotes for the TaqI B2 allele experienced a first MI 2 years later than men with other genotypes, 59 versus 61 years (P<0.05). This effect was not seen for the promoter polymorphism. These results strongly confirm the role of the CETP gene and the TaqIB variant as a risk factor for MI and suggest that another functional polymorphism is yet to be discovered in the CETP gene, that will explain the effect on MI associated with TaqIB observed in this study.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.