on June 8, 2006
Published online before print June 8, 2006, doi: 10.1161/01.ATV.0000231523.19199.45
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Submitted on January 17, 2006
Accepted on May 24, 2006
Consistent Effects of Genes Involved in Reverse Cholesterol Transport on Plasma Lipid and Apolipoprotein Levels in CARDIA Participants
Kathy L.E. Klos *;
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.
* To whom correspondence should be addressed. 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.
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