%0 Journal Article %J Hum Mol Genet %D 2008 %T APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels. %A Klos, Kathy %A Shimmin, Lawrence %A Ballantyne, Christie %A Boerwinkle, Eric %A Clark, Andrew %A Coresh, Josef %A Hanis, Craig %A Liu, Kiang %A Sayre, Scott %A Hixson, James %K Adult %K Aged %K Animals %K Apolipoproteins %K Apolipoproteins E %K Black or African American %K Cholesterol %K Cholesterol, LDL %K Chromosomes, Human, Pair 19 %K Female %K Genotype %K Humans %K Hybrid Cells %K Male %K Mexican Americans %K Mice %K Middle Aged %K Polymorphism, Single Nucleotide %K United States %K White People %X

We characterized 102 kb of chromosome 19 containing the apolipoprotein (APO) E/C1/C4/C2 cluster and two flanking genes for common DNA variants associated with plasma low-density lipoprotein cholesterol (LDL-C) level. DNA variants were identified by comparing sequences of 48 haploid hybrid cell lines. We genotyped participants (1943 Whites and 2046 African-Americans) of the Coronary Artery Risk Development in Young Adults study for 115 variants. After controlling for the effects of the APOE epsilon2/3/4 polymorphism, a single nucleotide polymorphism, rs35136575, in the downstream hepatic control region 2 (HCR-2) was associated with LDL-C in Caucasians (P = 0.0004), accounting for 1% of variation. We genotyped rs35136575 in the Atherosclerosis Risk in Communities (ARIC) cohort (3679 African-Americans and 10 427 Whites) and in the Genetic Epidemiology Network of Arteriopathy (GENOA) sibships (1381 African-Americans in 592 sibships, 1116 Caucasians in 503 sibships and 1378 Mexican-Americans in 416 sibships), finding association with LDL-C level in ARIC Caucasians (P = 0.0064). Lower plasma LDL-C was observed with the rare allele. Plasma apoE level was strongly associated with HCR-2 variant genotype in all three GENOA samples (P %B Hum Mol Genet %V 17 %P 2039-46 %8 2008 Jul 01 %G eng %N 13 %1 https://www.ncbi.nlm.nih.gov/pubmed/18378515?dopt=Abstract %R 10.1093/hmg/ddn101