The Effect of Polymorphisms in Candidate Genes on the Long-Term Risk of Lipodystrophy and Dyslipidemia in HIV-Infected White Patients Starting Antiretroviral Therapy

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-alpha, 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)-alpha 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. RI De Luca, Andrea/G-8810-2011