An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/low HDL levels in treated HIV patients

被引:106
作者
Fauvel, J
Bonnet, E
Ruidavets, JB
Ferrières, J
Toffoletti, A
Massip, P
Chap, H
Perret, B
机构
[1] Toulouse Univ Hosp, Lab Biochim 3, Toulouse, France
[2] Toulouse Univ Hosp, INSERM, U326, IFR 30,Inst Claude Preval, Toulouse, France
[3] Toulouse Univ Hosp, Serv Malad Infect, Toulouse, France
[4] Toulouse Univ Hosp, INSERM, U558, Toulouse, France
关键词
protease inhibitor; dyslipidaemia; apolipoprotein C-III; polymorphism; lipoparticle;
D O I
10.1097/00002030-200112070-00007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. Objectives: 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. Design: 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/F and Sstl) 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 haplotyes. 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. (C) 2001 Lippincott Williams & Wilkins.
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收藏
页码:2397 / 2406
页数:10
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