title: An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/low HDL levels in treated HIV patients.
abstract: BACKGROUND
  Long-term therapy with protease inhibitors (PI) is associated with hypertriglyceridaemia, low high-density lipoprotein (HDL) levels and accumulation of apolipoprotein (apo) E- and apo C-III-containing lipoproteins.
  
  
  OBJECTIVE
  To evaluate the impact, on this dyslipaemic phenotype, of three polymorphisms of the apo C-III gene: two on an insulin response element and one in the 3'-region. Apo E genotypes were evaluated also.
  
  
  METHODS
  Sixty consecutive male patients attending the HIV follow-up consultation were included during a 3-month period. All patients received at least one PI. Apo C-III and apo E genotypes were determined. Besides routine bio-clinical examination, a detailed exploration of lipoproteins and of insulin secretion markers was carried out.
  
  
  METHODS
  Plasma lipoparticles, insulin, proinsulin and C-peptide were measured by specific immuno-assays. Determination of apo C-III genotypes (-455C/T, -482C/T and SstI) and of apo E alleles (epsilon2, epsilon3 and epsilon4) were performed by amplification and endonuclease digestion and were confirmed by allele-specific oligonucleotide hybridization.
  
  
  RESULTS
  Distribution of apo C-III alleles defined four major haplotypes. Carriers of the -455C variant had 30% lower levels of HDL-cholesterol than non-carriers. Plasma triglycerides increased according to the number of variant alleles. In multivariate analysis, a model including age, body mass index, clinical stage and treatment length, plasma insulin and apo C-III haplotypes explained around 43% of the HDL-cholesterol and triglycerides variability. Measurements of lipids before and after the use of PI demonstrated synergistic effects of the treatment and apo C-III variants on triglyceride levels.
  
  
  CONCLUSIONS
  Apo C-III polymorphisms might identify a genetic predisposition to develop dyslipidaemia under PI therapy.
authors.affiliation: Laboratoire de Biochimie III and INSERM U 326-IFR 30-Institut Claude de Préval, Toulouse University Hospital, Toulouse-Cédex, France.
authors.forename: J
authors.initials: J
authors.lastname: Fauvel
authors.forename: E
authors.initials: E
authors.lastname: Bonnet
authors.forename: J B
authors.initials: JB
authors.lastname: Ruidavets
authors.forename: J
authors.initials: J
authors.lastname: Ferrières
authors.forename: A
authors.initials: A
authors.lastname: Toffoletti
authors.forename: P
authors.initials: P
authors.lastname: Massip
authors.forename: H
authors.initials: H
authors.lastname: Chap
authors.forename: B
authors.initials: B
authors.lastname: Perret
mesh_terms: D000328:Adult; D000483:Alleles; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics* / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D011110:Polymorphism, Genetic; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood*
chemical_list: D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D011480:Protease Inhibitors; D014280:Triglycerides