Impact of genetic polymorphisms on the risk of lipid disorders in patients on anti-HIV therapy.
Active anti-HIV therapy can induce hypertriglyceridemia, low high-density lipoprotein (HDL) and insulin resistance, eventually accompanied by clinical lipodystrophy, associated loss of subcutaneous adipose tissue and an increase in abdominal adiposity. The frequency of these metabolic disorders is approximately 50% and host genetic factors might confer particular susceptibility. Variants of apolipoproteins (apo) A5 and C3, interacting with APOE genotypes, have been associated with the severity of antiretroviral therapy-induced dyslipidemia and with occurrence of lipodystrophy, and for APOC3, with objective criteria of fat redistribution. Genetic polymorphisms of the nuclear transcription-factor sterol response element-binding proteins (SREBP1c) and of tumor necrosis factor-alpha (TNFalpha) have yielded contrasting results. Other candidate genes will be explored to define a pharmacogenomic strategy to identify patients at high risk of metabolic disorders upon antiretroviral therapy.
Bonnet
Eric
E
INSERM U563, Department of Lipoproteins and Lipid Mediators, CHU, Toulouse, France.
Genoux
Annelise
A
Bernard
Jacques
J
Fauvel
Josette
J
Massip
Patrice
P
Perret
Bertrand
B
D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000235:genetics; D006801:Humans; D052439:Lipid Metabolism Disorders / Q000139:chemically induced* / Q000235:genetics; D011110:Polymorphism, Genetic; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D001053:Apolipoproteins; D017320:HIV Protease Inhibitors; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha