APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels.

TitleAPOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels.
Publication TypeJournal Article
Year of Publication2008
AuthorsKlos, K, Shimmin, L, Ballantyne, C, Boerwinkle, E, Clark, A, Coresh, J, Hanis, C, Liu, K, Sayre, S, Hixson, J
JournalHum Mol Genet
Volume17
Issue13
Pagination2039-46
Date Published2008 Jul 01
ISSN1460-2083
KeywordsAdult, African Americans, Aged, Animals, Apolipoproteins, Apolipoproteins E, Cholesterol, Cholesterol, LDL, Chromosomes, Human, Pair 19, European Continental Ancestry Group, Female, Genotype, Humans, Hybrid Cells, Male, Mexican Americans, Mice, Middle Aged, Polymorphism, Single Nucleotide, United States
Abstract

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

DOI10.1093/hmg/ddn101
Alternate JournalHum. Mol. Genet.
PubMed ID18378515
PubMed Central IDPMC2900905
Grant ListR01 HL072904 / HL / NHLBI NIH HHS / United States
R01 HL039107 / HL / NHLBI NIH HHS / United States
HL051021 / HL / NHLBI NIH HHS / United States
HL039107 / HL / NHLBI NIH HHS / United States
R01 HL072810 / HL / NHLBI NIH HHS / United States
P50 GM065509 / GM / NIGMS NIH HHS / United States
HL072904 / HL / NHLBI NIH HHS / United States
GM065509 / GM / NIGMS NIH HHS / United States
HL072810 / HL / NHLBI NIH HHS / United States
HL054457 / HL / NHLBI NIH HHS / United States
R01 HL072905 / HL / NHLBI NIH HHS / United States
HL072905 / HL / NHLBI NIH HHS / United States