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  • Title: [Genetic variation of the cholesterol ester transfer protein gene and the prevalence of coronary artery disease. The AtheroGene case control study].
    Author: Blankenberg S, Tiret L, Bickel C, Schlitt A, Jungmair W, Genth-Zotz S, Lubos E, Espinola-Klein C, Rupprecht HJ.
    Journal: Z Kardiol; 2004; 93 Suppl 4():IV16-23. PubMed ID: 15085362.
    Abstract:
    BACKGROUND: Various functional polymorphisms of the cholesteryl ester transfer protein ( CETP) gene influence CETP activity and the concentration of high-density lipoprotein (HDL) cholesterol. Beside other functional variants mainly the promoter polymorphism CETP/C-629A is currently discussed as a risk factor of coronary artery disease (CAD). We evaluated in a large case-control study the impact of various CETP genotypes and haplotypes on HDL concentration and the prevalence of CAD. METHODS AND RESULTS: In 1214 patients with documented CAD as well as 754 population controls we determined the CETP/C-629A, TaqIB, I405V, R451Q, and A373P polymorphisms. All genotypes have an impact on the HDL concentration; univariate genotype and haplotype analyses demonstrate a significant effect of A-allel carriers on the elevation of HDL concentration. In addition, among all genotypes determined, the C-629A polymorphism is associated with the prevalence of CAD in a codominant fashion. Homozygous A-allel carriers reveal a relative risk of 0.6 (95% CI 0.44-0.82; P = 0.005) compared to the wild type. Adjustment for classical risk factors did not alter this association significantly, whereas after controlling for HDL concentration no independent significance between CETP/C-629A genotype and prevalence of CAD was observed anymore. CONCLUSION: CETP genotypes have an significant but moderate impact on systemic HDL-cholesterol concentration. The A-allel of the CETP/C-629A polymorphism is associated with a reduced CAD risk. This risk reduction is probably mediated by elevated HDL-concentration. Whether genotyping of the CETP/C-629A polymorphism provides information over and above that obtained by HDL-cholesterol measurement has to be further investigated in various prospective studies.
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