We investigated whether polymorphisms in human candidate genes could be associated with a different risk of developing lipodystrophy and dyslipidemia in HIV-infected patients starting combination antiretroviral therapy (cART). Genomic DNA samples from white HIV-1-infected patients were analyzed for seven polymorphisms located in the MDR1, TNF-α, APM1, APOE, and LPL genes. Lipid data were retrospectively collected beginning with the initiation of cART. Lipodystrophy was assessed cross-sectionally and then prospectively. The association with lipodystrophy and National Cholesterol Evaluation Program Adult Treatment Panel III-defined lipid thresholds was analyzed using survival analysis and logistic regression. One-hundred and seventy-four patients were genotyped. In 151 patients assessed for lipodystrophy, MDR1 3435 T homozygosis was associated with a higher hazard (adjusted hazard ratio, aHR, versus CT 0.25; p=0.02) and tumor necrosis factor (TNF)-α 308 G homozygosis with a lower hazard (vs. AA aHR 2.14; p=0.04) of developing trunk fat accumulation after adjusting for gender and initial cART type. The TNF 238 GG genotype was associated with a higher risk of developing low HDL-cholesterol levels (adjusted odd ratio, aOR, 5.91; p=0.01) while patients carrying the LPL S477X mutation were at lower risk of reaching high non-HDL-cholesterol levels (aOR 0.39; p=0.05). The APOEe3/3 genotype patients were at lower risk (aOR 0.26, p=0.015), whereas the adiponectin 276 GT carriers were at higher risk of developing hypertriglyceremia (vs. GG aOR 3.10; p=0.04). Knowledge of the effect of genetic determinants on dyslipidemia and lipodystrophy may prompt the investigation of potential pathogenetic mechanisms and might eventually be used for guiding individualized treatment decisions.
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|Titolo:||The effect of polymorphisms in candidate genes on the long-term risk of lipodystrophy and dyslipidemia in HIV-infected white patients starting antiretroviral therapy|
|Citazione:||The effect of polymorphisms in candidate genes on the long-term risk of lipodystrophy and dyslipidemia in HIV-infected white patients starting antiretroviral therapy / Marzocchetti, A; Schwarz, J; DI GIAMBENEDETTO, S; Colafigli, M; Bracciale, L; Fabbiani, M; Fantoni, M; Trecarichi, Em; Cauda, R; DE LUCA, Andrea. - In: AIDS RESEARCH AND HUMAN RETROVIRUSES. - ISSN 0889-2229. - 27:12(2011), pp. 1299-1309.|
|Appare nelle tipologie:||1.1 Articolo in rivista|