title: Plasma concentration and lipoprotein distribution of ApoC-I is dependent on ApoE genotype rather than the Hpa I ApoC-I promoter polymorphism.
abstract: An Hpa I restriction site located 317 bp upstream of the transcription initiation site of the apoC-I gene has been shown to increase apoC-I gene transcription in vitro. The aim of the present study was to determine whether this genetic polymorphism was associated in vivo with increased plasma levels of apoC-I. In a cohort of French-Canadians (n=391) recruited for a family study, we found strong linkage disequilibrium between the genes for apoC-I and apoE (as reported before for European-Americans), such that the apoC-I Hpa I-negative (H1) allele was strongly associated with apoE epsilon 3, whereas the apoC-I Hpa I-positive (H2) allele was strongly associated with apoE epsilon 2 and epsilon 4. ApoC-I and apoE were measured by ELISA in total plasma and in very low-density lipoproteins (VLDL) separated by ultracentrifugation (d<1.006 g/ml), and then by difference for the non-VLDL fraction (d>1.006 g/ml), in a subset of families selected for their diverse apoE genotypes. Subjects were divided into normolipidemic (NL, n=89, TG<2.3 mmol/l, LDL-C<3.8 mmol/l) and hyperlipidemic groups (HL, n=88, TG>2.3 mmol/l and/or LDL-C>3.8 mmol/l). In NL subjects, apoC-I levels were not significantly associated with apoC-I genotype (H1/H1, H1/H2 or H2/H2). They were, however, related to apoE genotype, such that apoE3/2 subjects tended to have higher and apoE4/3 subjects tended to have lower concentrations of total plasma and non-VLDL apoC-I and apoE. Total plasma, VLDL and non-VLDL apoC-I and E levels were also higher in HL subjects with an apoE2/2 or apoE3/2 genotype. These results suggest that plasma levels of apoC-I are more strongly influenced by apoE genotype than by the Hpa I apoC-I promoter polymorphism, which probably reflects an effect of different apoE isoforms on plasma lipoprotein and plasma apoC-I metabolism, rather than a direct effect of apoE alleles on apoC-I transcription.
authors.affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal, 110 Pine Avenue West, Montréal, Québec, Canada H2W 1R7. cohnj@ircm.qc.ca
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Cohn
authors.forename: Michel
authors.initials: M
authors.lastname: Tremblay
authors.forename: Lucie
authors.initials: L
authors.lastname: Boulet
authors.forename: Hélène
authors.initials: H
authors.lastname: Jacques
authors.forename: Jean
authors.initials: J
authors.lastname: Davignon
authors.forename: Madeleine
authors.initials: M
authors.lastname: Roy
authors.forename: Lise
authors.initials: L
authors.lastname: Bernier
mesh_terms: D000328:Adult; D000483:Alleles; D053302:Apolipoprotein C-I; D001056:Apolipoproteins C / Q000032:analysis / Q000097:blood* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D002170:Canada; D005260:Female; D005602:France / Q000208:ethnology; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008079:Lipoproteins, VLDL / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D053302:Apolipoprotein C-I; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008055:Lipids; D008079:Lipoproteins, VLDL