title: Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis.
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.
authors.affiliation: Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN 55455, United States. tsaix001@umn.edu
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: Craig
authors.initials: C
authors.lastname: Johnson
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Arends
authors.forename: Richard
authors.initials: R
authors.lastname: Kronmal
authors.forename: Nancy Swords
authors.initials: NS
authors.lastname: Jenny
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
authors.forename: Donna
authors.initials: D
authors.lastname: Arnett
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Leary
authors.forename: Wendy
authors.initials: W
authors.lastname: Post
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D050197:Atherosclerosis / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL