[Toxicogenetics of antiretroviral treatment (1): lipodystrophy, metabolic perturbations and atherosclerosis].
Among the adverse effects attributed to antiretroviral therapy, one of the most striking is probably the appearance of the lipodystrophy syndrome and its associated metabolic derangements, given its potential long-term effect as a cardiovascular risk factor. Since not all patients who receive antiretroviral drugs experience these adverse effects, a host genetic predisposition has been postulated. However, currently available data on this issue is inconclusive and preliminary. It has been consistently demonstrated that polymorphisms in the genes that encode for apolipoproteins A5, C3 and E, for the cholesterol ester transporter proteins (CETP), and in the ATP binding cassette type A1 (ABCA1) influence the development of dyslipidemia in patients treated with antiretroviral drugs, particularly if the therapeutic regimen includes protease inhibitors. Data on the effect of polymorphisms in the sterol regulatory ester binding protein type 1 (SREBP1) are inconsistent. The effect of mitochondrial DNA mutations on the risk of lipodystrophy has been assessed, with inconclusive data. No polymorphisms in the lamin A gene have been detected. Investigations have assessed the effect of diverse polymorphisms in the genes that encode for several proinflammatory cytokines such as tumour necrosis factor alpha (TNF-alpha), interleukin-1-beta (IL-1beta) and interleukin-6 (IL-6). The results show inconsistent data in the case of TNF-alpha, no association in the case of IL-6, and preliminary positive associations in IL-1beta. In contrast, polymorphisms in the genes encoding for stromal derived factor 1 (SDF-1) and for monocyte chemoattractant protein 1 (MCP-1) have been shown to influence the development of subclinical atherosclerosis in HIV-1-infected patients treated with antiretroviral drugs.
Gutiérrez Maciá
M Mar
MM
Unidad de Enfermedades Infecciosas, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, España.
Mateo García
M Gracia
MG
Vidal Marsal
Francesc
F
Domingo Pedrol
Pere
P
D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000235:genetics; D006801:Humans; D008659:Metabolic Diseases / Q000139:chemically induced / Q000235:genetics; D011110:Polymorphism, Genetic; D043922:Toxicogenetics
D044966:Anti-Retroviral Agents