title: Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. whites and African blacks.
abstract: Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE*2 and APOE*4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Zaheda H
authors.initials: ZH
authors.lastname: Radwan
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Fahad
authors.initials: F
authors.lastname: Waqar
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Dilek
authors.initials: D
authors.lastname: Pirim
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Vipavee
authors.initials: V
authors.lastname: Niemsiri
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hamman
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Clareann H
authors.initials: CH
authors.lastname: Bunker
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: F Yesim
authors.initials: FY
authors.lastname: Demirci
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics; D044383:Black People / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood*; D014481:United States; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides