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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1828.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Consistent Effects of Genes Involved in Reverse Cholesterol Transport on Plasma Lipid and Apolipoprotein Levels in CARDIA Participants

Kathy L.E. Klos; Charles F. Sing; Eric Boerwinkle; Sara C. Hamon; Thomas J. Rea; Andrew Clark; Myriam Fornage; James E. Hixson

From Human Genetics Center (K.L.E.K., E.B., J.E.H.), University of Texas Health Science Center, Houston, Tex; Department of Human Genetics (C.F.S., T.J.R.), University of Michigan, Ann Arbor, Mich; Institute of Molecular Medicine (E.B., M.F.), University of Texas Health Science Center, Houston, Tex; Rockefeller University (S.C.H.), New York, NY; Department of Molecular Biology and Genetics (A.C.), Cornell University, Ithaca, NY.

Correspondence to Dr Kathy L.E. Klos, University of Texas Health Science Center at Houston, School of Public Health, Human Genetics Center, P.O. Box 20186, Houston, TX 77225.E-mail kathy.klos{at}uth.tmc.edu

Objective— To identify common variations in genes in the reverse cholesterol transport pathway with nongender-specific influence on plasma lipid and apolipoprotein levels.

Methods and Results— An average of 5 single nucleotide polymorphisms (SNPs) were genotyped within each of 45 genomic regions (54 genes) in blacks (1131 females and 812 males) and whites (1102 females and 954 males) from the Coronary Artery Risk Development in Young Adults (CARDIA) study. SNPs and gene-based 3-SNP haplotypes were evaluated for their ability to predict variation in plasma apolipoproteins (apo) A-I and apoB, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides (TG). We identified 14 SNPs in 6 candidate gene regions that explained statistically significant variation in the same trait in both genders of at least one race and with evidence of consistent genotype mean trend across gender within race. Haplotype analyses identified 9 candidate gene regions that explained statistically significant variation in one or both races.

Conclusion— Four gene regions, ABCA1, APOA1/C3/A4/A5, APOE/C1/C4/C2, and CETP, explained plasma lipoprotein variation most consistently across strata. Other gene regions that influence plasma lipid and apolipoprotein levels within race include CYP7A1, LPL, PPARA, SOAT1, and SREBF2.

To identify common gene variations with a consistent influence we evaluated 262 SNPs in 54 genes for association with 6 plasma lipid and apolipoprotein traits. We identified 14 SNPs and 9 gene regions with genotype effects.

Key Words: lipids • genetics of cardiovascular disease • lipid and lipoprotein metabolism

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