Journal Article

Genetic Factors Influencing Severe Atazanavir-Associated Hyperbilirubinemia in a Population with Low UDP-Glucuronosyltransferase 1A1*28 Allele Frequency

Wan Beom Park, Pyoeng Gyun Choe, Kyoung-Ho Song, Jae Hyun Jeon, Sang Won Park, Hong Bin Kim, Nam Joong Kim, Myoung-don Oh and Kang Won Choe

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 1, pages 101-106
Published in print July 2010 | ISSN: 1058-4838
Published online July 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/653427
Genetic Factors Influencing Severe Atazanavir-Associated Hyperbilirubinemia in a Population with Low UDP-Glucuronosyltransferase 1A1*28 Allele Frequency

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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/µL (interquartile range, 181–405 cells/µL). 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/µL 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.

Journal Article.  3649 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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