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Common variation in the CETP gene and the implications for cardiovascular disease and its treatment: an updated

Robin P F Dullaart1, Wim J Sluiter

  • 1Department of Endocrinology, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. r.p.f.dullaart@int.umcg.nl

Pharmacogenomics
|June 4, 2008
PubMed

Insights

The cholesteryl ester transfer protein (CETP) TaqIB polymorphism

Area of Science:

  • Genetics and cardiovascular disease epidemiology

Background:

  • Human plasma contains cholesteryl ester transfer protein (CETP), which influences HDL cholesterol levels.
  • The CETP gene TaqIB polymorphism (rs708272) is common, with B2B2 carriers exhibiting higher HDL cholesterol than B1B1 carriers.
  • The association between this polymorphism and cardiovascular disease (CVD) risk remains unclear.

Purpose of the Study:

  • To conduct a pooled analysis of Caucasian subjects to clarify the association between the CETP TaqIB polymorphism and CVD risk.
  • To investigate potential differences in genotype distribution and CVD risk between population-based and high-risk populations.
  • To explore the polymorphism's role in predicting response to lipid-lowering treatments and diet interventions.

Main Methods:

  • Pooled analysis of published studies comprising predominantly Caucasian subjects.
  • Comparison of CETP TaqIB genotype distribution in population-based studies (n=10,526) versus high-risk populations (n=10,947).
  • Calculation of odds ratios (OR) for CVD in relation to CETP TaqIB genotypes in different study populations.

Main Results:

  • Genotype distribution differed significantly between population-based and high-risk cohorts (p=0.0009), with fewer B2B2 carriers in high-risk groups.
  • In population-based studies, B2B2 carriers had a higher CVD risk (OR=1.45) compared to B1B1 carriers.
  • Conversely, in high-risk populations, B2B2 carriers showed a lower CVD risk (OR=0.84) compared to B1B1 carriers.
  • Contradictory results were found regarding the polymorphism's ability to predict treatment efficacy or lipid response to diet.

Conclusions:

  • The CETP TaqIB polymorphism's association with CVD risk appears dependent on the study population.
  • The B2 allele may be associated with increased CVD risk in the general population, despite higher HDL cholesterol.
  • Observed protective effects in high-risk populations might be due to selection bias against B2B2 homozygotes.

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