Comprehensive evaluation of apolipoprotein H gene (APOH) variation identifies novel associations with measures of lipid metabolism in GENOA.

TitleComprehensive evaluation of apolipoprotein H gene (APOH) variation identifies novel associations with measures of lipid metabolism in GENOA.
Publication TypeJournal Article
Year of Publication2008
AuthorsLeduc, MS, Shimmin, LC, Klos, KLE, Hanis, C, Boerwinkle, E, Hixson, JE
JournalJ Lipid Res
Volume49
Issue12
Pagination2648-56
Date Published2008 Dec
ISSN0022-2275
KeywordsAfrican Continental Ancestry Group, beta 2-Glycoprotein I, European Continental Ancestry Group, Genetic Variation, Genotype, Haplotypes, Humans, Lipid Metabolism, Multicenter Studies as Topic, Polymorphism, Single Nucleotide
Abstract

Apolipoprotein H (apoH, also named beta-2 glycoprotein I) is found on several classes of lipoproteins, and is involved in the activation of lipoprotein lipase in lipid metabolism. We have comprehensively investigated the association of variation in the apoH gene (APOH) with lipid traits in hepatic cholesterol transport, dietary cholesterol transport (DCT), and reverse cholesterol transport (RCT). Our study population consisted of families from the Genetic Epidemiology Network of Arteriopathy multicenter study that include African Americans, Mexican Americans, and European Americans. We individually tested 36 single-nucleotide polymorphisms (SNPs) that span the APOH locus, including nonsynonymous variants that result in known apoH charge isoforms. In addition, we constructed haplotypes from SNPs in the 5' promoter region that comprise cis-acting regulatory elements, as well as haplotypes for multiple amino acid substitutions. We found point-wise significant associations of APOH variants with various lipid measures in the three racial groups. The strongest associations were found for DCT traits (triglyceride and apoE levels) in Mexican Americans with a nonsynonymous variant (SNP 14917, Cys306Gly) that may alter apoH protein folding in a region involved in phospholipid binding. In conclusion, family-based analyses of APOH variants have identified associations with measures of lipid metabolism in three American racial groups.

DOI10.1194/jlr.M800155-JLR200
Alternate JournalJ Lipid Res
PubMed ID18676959
PubMed Central IDPMC2582370
Grant ListR01 HL039107 / HL / NHLBI NIH HHS / United States
HL-051021 / HL / NHLBI NIH HHS / United States
U01 HL054504 / HL / NHLBI NIH HHS / United States
U10 HL054504 / HL / NHLBI NIH HHS / United States
R01 HL072810 / HL / NHLBI NIH HHS / United States
R37 HL051021-12 / HL / NHLBI NIH HHS / United States
R37 HL051021-13 / HL / NHLBI NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
U01 HL054457 / HL / NHLBI NIH HHS / United States
R37 HL051021-11 / HL / NHLBI NIH HHS / United States
HL-039107 / HL / NHLBI NIH HHS / United States
HL-054457 / HL / NHLBI NIH HHS / United States
HL-072810 / HL / NHLBI NIH HHS / United States
HL-54504 / HL / NHLBI NIH HHS / United States
R37 HL051021-14 / HL / NHLBI NIH HHS / United States
R37 HL051021-15 / HL / NHLBI NIH HHS / United States
R37 HL051021 / HL / NHLBI NIH HHS / United States
R37 HL051021-10 / HL / NHLBI NIH HHS / United States