title: Short communication: UGT1A1*28 variant allele is a predictor of severe hyperbilirubinemia in HIV-infected patients on HAART in southern Brazil.
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.
authors: Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, RS, Brazil.
authors: Lisiane
authors: L
authors: Turatti
authors: Eduardo
authors: E
authors: Sprinz
authors: Rosmeri K
authors: RK
authors: Lazzaretti
authors: Regina
authors: R
authors: Kuhmmer
authors: Grasiela
authors: G
authors: Agnes
authors: Jussara M
authors: JM
authors: Silveira
authors: Rossana P
authors: RP
authors: Basso
authors: Cezar A T
authors: CA
authors: Pinheiro
authors: Mariângela F
authors: MF
authors: Silveira
authors: Silvana
authors: S
authors: de Almeida
authors: Jorge P
authors: JP
authors: Ribeiro
authors: Vanessa S
authors: VS
authors: Mattevi
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods; D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood* / Q000235:genetics; D001938:Brazil; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000187:drug effects* / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D019469:Indinavir / Q000009:adverse effects*; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects*; D011237:Predictive Value of Tests; D011725:Pyridines / Q000009:adverse effects*; D012307:Risk Factors; D012720:Severity of Illness Index; D000099148:UGT1A1 Enzyme
chemical_list: D000069446:Atazanavir Sulfate; D001663:Bilirubin; D014453:Glucuronosyltransferase; D017320:HIV Protease Inhibitors; D019469:Indinavir; D009842:Oligopeptides; D011725:Pyridines; D000099148:UGT1A1 Enzyme