CETP gene variation: relation to lipid parameters and cardiovascular risk.

Authors: Boekholdt SM; Kuivenhoven JA; Hovingh GK; Jukema JW; Kastelein JJ; van Tol A

Abstract: PURPOSE OF REVIEW: Over the past decade lowering of low-density lipoprotein-cholesterol levels has been established as the foundation for preventing coronary artery disease, but substantial additional risk reduction remains to be gained by modifying risk factors other than low-density lipoprotein-cholesterol. Raising high-density lipoprotein-cholesterol levels by inhibiting activity of the cholesteryl ester transfer protein (CETP) is a prime target. Research on naturally occurring variants in the CETP gene has yielded numerous insights that have been relevant for understanding lipoprotein metabolism, and crucial to the development of pharmacological CETP inhibition. RECENT FINDINGS: This review discusses a number of recently published studies, including a haplotype analysis of the CETP promoter region confirming that the -629 C-->A variant, not the TaqIB variant, is instrumental in determining CETP activity, as previously suggested. In addition, we discuss a recent meta-analysis which confirms that the I405V and TaqIB variants are indeed associated with lower CETP activity and higher high-density lipoprotein-cholesterol levels. Also, we review two subanalyses of large randomized controlled pravastatin trials which found no evidence for a proposed pharmacogenetic interaction between the CETP TaqIB variant and pravastatin treatment. SUMMARY: The currently available evidence suggests that several genetic variants in the CETP gene are associated with altered CETP plasma levels and activity, high-density lipoprotein-cholesterol plasma levels, low-density lipoprotein and high-density lipoprotein particle size, and perhaps the risk of coronary artery disease. No evidence exists for a pharmacogenetic interaction between the CETP TaqIB variant and pravastatin efficacy.

Keywords: Cardiovascular Diseases/*genetics; Carrier Proteins/*genetics; Cholesterol/metabolism; Cholesterol Ester Transfer Proteins; Cholesterol, HDL/metabolism; Coronary Vessels/pathology; *Genetic Variation; Genotype; Glycoproteins/*genetics; Humans; *Lipid Metabolism; Lipoproteins, HDL/metabolism; Mutation; Pravastatin/therapeutic use
Journal: Current opinion in lipidology
Volume: 15
Issue: 4
Pages: 393-8
Date: July 10, 2004
PMID: 15243211
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Citation:

Boekholdt SM, Kuivenhoven JA, Hovingh GK, Jukema JW, Kastelein JJ, van Tol A (2004) CETP gene variation: relation to lipid parameters and cardiovascular risk. Current opinion in lipidology 15: 393-8.


Lifespan Factors:
  • CETP cholesteryl ester transfer protein, plasma


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