title: Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study.
abstract: In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study. Both univariate and multivariate apoA-V levels showed no association with future CAD (P = 0.4 and 0.5, respectively). Unexpectedly, there was a significant positive correlation between serum apoA-V and TG in men and women (r = 0.36 and 0.28, respectively, P < 0.001 each) but a negative correlation between apoA-V and LPL mass (r = -0.14 and -0.12 for men and women respectively, P < 0.001 each). The frequency of the c.56C>G polymorphism did not differ between cases and controls despite significant positive association of c.56G with both apoA-V and TG levels. For -1131T>C, the minor allele was significantly associated with lower apoA-V yet higher TG levels and was overrepresented in cases (P = 0.047). The association of -1131T>C with CAD risk, however, was independent of apoA-V levels and likely acts through linkage disequilibrium with APOC3 variants. The positive correlation of apoA-V levels with TG levels, negative correlation with LPL levels, and lack of association with CAD risk highlight the need for further human studies to clarify the role of apoA-V.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Stefan F C
authors.initials: SF
authors.lastname: Vaessen
authors.forename: Frank G
authors.initials: FG
authors.lastname: Schaap
authors.forename: Jan-Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
authors.forename: Robert
authors.initials: R
authors.lastname: Luben
authors.forename: Jutta A
authors.initials: JA
authors.lastname: Palmen
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
mesh_terms: D000368:Aged; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics; D001054:Apolipoproteins A; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D006113:United Kingdom
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D014280:Triglycerides