alexa Short communication: UGT1A1*28 variant allele is a predictor of severe hyperbilirubinemia in HIV-infected patients on HAART in southern Brazil.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Turatti L, Sprinz E, Lazzaretti RK, Kuhmmer R, Agnes G,

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Abstract Highly active antiretroviral therapy (HAART) has increased the survival of HIV-infected patients. However, adverse effects play a major role in adherence to HAART. Some protease inhibitors (mainly atazanavir and indinavir) act as inhibitors of uridine diphosphate-glucuronosyltransferase (UGT1A1), the enzyme responsible for hepatic conjugation of bilirubin. Variations in the promoter region of the UGT1A1 gene (UGT1A1*28, rs8175347) can influence bilirubin plasma levels, modulating the susceptibility to hyperbilirubinemia. Aiming to analyze the association between UGT1A1*28 allele and hyperbilirubinemia in individuals exposed to HAART, we evaluated 375 HIV-positive individuals on antiretroviral therapy. Individuals carrying the UGT1A1*28 allele had a higher risk of developing severe hyperbilirubinemia [prevalence ratio (PR)=2.43, 95\% confidence interval (CI) 1.08-5.45, p=0.032] as well as atazanavir users (PR=7.72, 95\% CI=3.14-18.98, p<0.001). This is the first description of such an association in Brazilian HIV patients, which shows that in African-American and Euroamerican HAART users, the UGT1A1*28 allele also predisposes to severe hyperbilirubinemia, especially in those exposed to atazanavir. This article was published in AIDS Res Hum Retroviruses and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

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