Cholesteryl ester transfer protein gene effect on CETP activity and plasma high‐density lipoprotein in European populations

作者：Vilmundur G. Gudnason, Sakari Kakko, Viviane Nicaud, Markku J. Savolainen, Y. Antero Kesäniemi, Esa Tahvanainen, Steve Eric Humphries, On Behalf Of The Ears Group · 发表于：European Journal of Clinical Investigation · 年份：1999 · DOI：10.1046/j.1365-2362.1999.00412.x · 被引用次数：132 · 研究领域：Diabetes, Cardiovascular Risks, and Lipoproteins、Lipoproteins and Cardiovascular Health、Peroxisome Proliferator-Activated Receptors

BACKGROUND: Variation at the cholesteryl ester transfer protein (CETP) gene locus has been implicated in determining the levels and activity of CETP, apoAI and high-density lipoprotein (HDL) plasma concentration and the risk of developing coronary artery disease. STUDY DESIGN: The effects of two common polymorphisms of CETP, TaqIB in intron 1 and isoleucine 405 to valine (I405-->V) in exon 14, were examined in a sample of 822 men age 18-28 years from 11 countries in Europe who had participated in a study (the European Atherosclerosis Research Study II) of the offspring of myocardial infarction sufferers before the age of 55 years and age-matched control subjects. RESULTS: The frequency of the rare TaqIB allele (B2) and the rare V405 allele was 0.44 and 0.28 respectively and was the same in different regions of Europe. There was a moderate linkage disequilibrium between the two polymorphisms in all the regions (D' = +0.31, P < 0.001), explained by the preferential association between the two common alleles, B1 and I405. There was a statistically significant association of the rare alleles for both the polymorphisms with lower activity of CETP (P < 0.001), 11.2% lower for the TaqIB and 7.0% lower for the I405-->V polymorphism. The TaqIB polymorphism explained 9.1% (P < 0.001) and I405-->V explained 3.7% (P < 0.001) of the variance in CETP activity, and in combination these genotypes explained 12.0% of the variance (P < 0.001). Overall, subjects whose fathers had had an early co...