title: An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.
abstract: Comparison of genomic DNA sequences from human and mouse revealed a new apolipoprotein (APO) gene (APOAV) located proximal to the well-characterized APOAI/CIII/AIV gene cluster on human 11q23. Mice expressing a human APOAV transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoav had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across the APOAV locus were found to be significantly associated with plasma triglyceride levels in two independent studies. These findings indicate that APOAV is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.
authors.affiliation: Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Pennacchio
authors.forename: M
authors.initials: M
authors.lastname: Olivier
authors.forename: J A
authors.initials: JA
authors.lastname: Hubacek
authors.forename: J C
authors.initials: JC
authors.lastname: Cohen
authors.forename: D R
authors.initials: DR
authors.lastname: Cox
authors.forename: J C
authors.initials: JC
authors.lastname: Fruchart
authors.forename: R M
authors.initials: RM
authors.lastname: Krauss
authors.forename: E M
authors.initials: EM
authors.lastname: Rubin
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000235:genetics* / Q000502:physiology*; D001054:Apolipoproteins A; D001056:Apolipoproteins C / Q000097:blood; D002880:Chromosomes, Human, Pair 11; D015331:Cohort Studies; D019295:Computational Biology; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D005810:Multigene Family; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D019076:Transgenes; D014280:Triglycerides / Q000097:blood*
chemical_list: C437704:APOA5 protein, human; C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D008079:Lipoproteins, VLDL; D014280:Triglycerides