Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

Michael Y. Tsai, Craig Johnson, W. H Linda Kao, A. Richey Sharrett, Valerie L. Arends, Richard Kronmal, Nancy Swords Jenny, David R. Jacobs, Donna Arnett, Daniel O'Leary, Wendy Post

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

The cholesteryl ester transfer protein (CETP) plays a key role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP activity and concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration; however, controversies remain about whether these genetic variants are associated with atherosclerosis. We genotyped the CETP R451Q, A373P, -629C/A, Taq1B, and -2505C/A polymorphisms in a cohort of Caucasian, Chinese, African-American, and Hispanic individuals within the Multi-Ethnic Study of Atherosclerosis. Genotypes were examined in relationship to HDL-C, CETP activity, CETP concentration, and three measures of subclinical cardiovascular disease (CVD): coronary artery calcium (CAC) measured by fast CT scanning, carotid intimal-medial thickness (IMT), and carotid artery plaque measured by ultrasonography. Carriers of the 451Q and 373P alleles have a significantly higher CETP concentration (22.4% and 19.5%, respectively; p < 0.001) and activity (13.1% and 9.4%, respectively; p < 0.01) and lower HDL-C (5.6% and 6.0%, respectively; p < 0.05). The minor alleles of the R451Q and A373P polymorphisms are associated with the presence of CAC, even after adjusting for CVD risk factors and HDL-C (p = 0.006 and p = 0.01, respectively). The R451Q polymorphism is also associated with presence of carotid artery plaque (p = 0.036). Polymorphism is associated with neither common nor internal carotid IMT. We confirmed that the -629A, Taq1B B2, and -2505A alleles are significantly associated with lower CETP concentration (20.8%, 25.0%, and 23.7%, respectively; p < 0.001) and activity (14.8%, 19.8%, and 18.4%, respectively; p < 0.001) and higher HDL-C concentration (9.7%, 11.5%, and 10.4%, respectively; p < 0.01). However, we did not find any associations between these non-coding polymorphisms and subclinical CVD.

Original languageEnglish (US)
Pages (from-to)359-367
Number of pages9
JournalAtherosclerosis
Volume200
Issue number2
DOIs
StatePublished - Oct 2008

Bibliographical note

Funding Information:
This research was supported by contracts N01-HC-95159 through N01-HC-95167 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org .

Keywords

  • CETP
  • CVD
  • HDL
  • MESA

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