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

Cited 36 time in Web of Science Cited 39 time in Scopus
Authors
Park, Wan Beom; Choe, Pyoeng Gyun; Song, Kyoung-Ho; Jeon, Jae Hyun; Kim, Hong Bin; Oh, Myoung-Don; Choe, Kang Won; Kim, Nam Joong; Park, Sang Won
Issue Date
2010-07-01
Publisher
OXFORD UNIV PRESS INC
Citation
CLINICAL INFECTIOUS DISEASES; Vol.51 1; 101-106
Abstract
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/mu L (interquartile range, 181-405 cells/mu L). 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/mu L 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.
ISSN
1058-4838
Language
English
URI
https://hdl.handle.net/10371/76615
DOI
https://doi.org/10.1086/653427
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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