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Genetic factors influencing severe atazanavir-associated hyperbilirubinemia in a population with low UDP-glucuronosyltransferase 1A1*28 allele frequency.

Author(s): Park WB, Choe PG, Song KH, Jeon JH, Park SW, Kim HB, Kim NJ, Oh MD, Choe KW

Affiliation(s): Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Publication date & source: 2010-07-01, Clin Infect Dis., 51(1):101-6.

Publication type: Research Support, Non-U.S. Gov't

BACKGROUND: High prevalence of severe atazanavir-associated hyperbilirubinemia in Asians with low prevalence of the UDP-glucuronosyltransferase (UGT)1A1*28 polymorphism suggests the importance of genetic factors other than UGT1A1*28 for atazanavir-associated hyperbilirubinemia in these populations. METHODS: Serum bilirubin levels were measured in 129 Korean human immunodeficiency virus-infected patients 3 months after initiation of atazanavir (400 mg per day) with good adherence to medication. The multidrug resistance gene 1 (MDR1) C3435T and G2677T/A variations and UGT1A1*6 and *28 were examined by direct sequencing of DNA from peripheral whole blood samples. The associations between genetic polymorphisms and severe (grade 3-4) hyperbilirubinemia were evaluated using multivariate logistic regression analysis including demographic and clinical variables. RESULTS: The median patient age was 39 years (interquartile range, 34-51 years), and 91% were men. At baseline, the median CD4 cell count was 261 cells/microL (interquartile range, 181-405 cells/microL). Severe hyperbilirubinemia was detected in 27 patients (21%). The independent risk factors for severe hyperbilirubinemia were low baseline CD4 cell count (adjusted odds ratio per 10 cells/microL increase, 0.97; 95% confidence interval, 0.94-0.99), UGT1A1*28 (adjusted odds ratio, 4.15; 95% confidence interval, 1.46-11.84), and MDR1 G2677T/A (adjusted odds ratio, 9.65; 95% confidence interval, 1.09-85.61). Of 19 patients with wild-type alleles for both MDR1 2677 and UGT1A1*28, none developed severe hyperbilirubinemia. CONCLUSION: The MDR1 G2677T/A variation and UGT1A1*28 are independent risk factors for severe atazanavir-associated hyperbilirubinemia in Korean human immunodeficiency virus-infected patients.

Page last updated: 2010-10-05

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