Cholesteryl ester transfer protein gene effect on CETP activity and plasmahigh-density lipoprotein in European populations

Citation
V. Gudnason et al., Cholesteryl ester transfer protein gene effect on CETP activity and plasmahigh-density lipoprotein in European populations, EUR J CL IN, 29(2), 1999, pp. 116-128
Citations number
63
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Journal title
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
00142972 → ACNP
Volume
29
Issue
2
Year of publication
1999
Pages
116 - 128
Database
ISI
SICI code
0014-2972(199902)29:2<116:CETPGE>2.0.ZU;2-Y
Abstract
Background Variation at the cholesteryl ester transfer protein (CETP) gene locus has been implicated in determining the levels and activity of CETP, a poAI and high-density lipoprotein (HDL) plasma concentration and the risk o f developing coronary artery disease. Study design The effects of two common polymorphisms of CETP, TaqIB in intr on 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 pa rticipated in a study (the European Atherosclerosis Research Study II) of t he 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 allel e was 0.44 and 0.28 respectively and was the same in different regions of E urope. There was a moderate linkage disequilibrium between the two polymorp hisms in all the regions (D' = +0.31, P < 0.001), explained by the preferen tial association between the two common alleles, B1 and I405. There was a s tatistically significant association of the rare alleles for both the polym orphisms 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 exp lained 9.1% (P < 0.001) and I405 --> V explained 3.7% (P < 0.001) of the va riance in CETP activity, and in combination these genotypes explained 12.0% of the variance (P < 0.001). Overall, subjects whose fathers had had an ea rly coronary heart disease had 2.4% higher plasma CETP activity than those without such family history, which became statistically significant when ad justed for the effect of the genotypes (P = 0.015), but the significance di sappeared after adjustment for the effect of lipids. There was a statistica lly significant effect of the TaqIB polymorphism on both plasma HDL cholest erol and apoAI level (P < 0.001), with those homozygous for the rare B2 all ele having the highest level. Those individuals homozygous for the rare V40 5 allele had the highest HDL and apoAI levels, although these effects only reached statistical significance for HDL (P < 0.03). Conclusion These results suggest that the TaqIB and I405 --> V polymorphism s represent two independent functional variations in the CETP gene that may affect the activity of CETP and thus plasma levels of HDL.