Journal
ATHEROSCLEROSIS
Volume 169, Issue 1, Pages 63-70Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/S0021-9150(03)00139-4
Keywords
triglyceride; cholesterol; atherosclerosis; lipoprotein metabolism
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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 (HI) allele was strongly associated with apoE E;3, whereas the apoC-I Hpa I-positive (1-12) allele was strongly associated with apoE epsilon2 and epsilon4. 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, it = 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/H2 or H2/H2). The), 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. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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