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Title: HLA-B* 3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients
Authors: Soranun Chantarangsu
Taisei Mushiroda
Surakameth Mahasirimongkol
Sasisopin Kiertiburanakul
Somnuek Sungkanuparph
Weerawat Manosuthi
Woraphot Tantisiriwat
Angkana Charoenyingwattana
Thanyachai Sura
Wasun Chantratita
Yusuke Nakamura
Faculty of Medicine
Mahidol University
Center for International Cooperation
Thailand Ministry of Public Health
Srinakharinwirot University
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 1-Feb-2009
Citation: Pharmacogenetics and Genomics. Vol.19, No.2 (2009), 139-146
Abstract: Objective Investigation of a possible involvement of differences in human leukocyte antigens (HLA) in the risk of nevirapine (NVP)-mduced skin rash among HIV-infected patients. Methods A step-wise case-control association study was conducted. The first set of samples consisted of 80 samples from patients with NVP-induced skin rash and 80 samples from NVP-tolerant patients. These patients were genotyped for the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 by a sequence-based HLA typing method. Subsequently, we verified HLA alleles that showed a possible association in the first screening using an additional set of samples consisting of 67 cases with NVP-induced skin rash and 105 controls. Results An HLA-B*3505 allele revealed a significant association with NVP-induced skin rash in the first and second screenings. In the combined data set, the HLA-B*3505 allele was observed in 17.5% of the patients with NVP-induced skin rash compared with only 1.1% observed in NVP-tolerant patients [odds ratio (OR) = 18.96; 95% confidence interval (Cl)=4.87-73.44, Pc=4.6 × 10 -6] and 0.7% in general Thai population (OR = 29.87; 95% Cl = 5.04-175.86, Pc=2.6 × 10 -5). The logistic regression analysis also indicated HLA-B*3505 to be significantly associated with skin rash with OR of 49.15 (95% Cl = 6.45-374.41, P= 0.00017). Conclusion A strong association between the HLA-B*3505 and NVP-induced skin rash provides a novel insight into the pathogenesis of drug-induced rash in the HIV-infected population. On account of its high specificity (98.9%) in identifying NVP-induced rash, it is possible to utilize the HLA-B*3505 as a marker to avoid a subset of NVP-induced rash, at least in Thai population. © 2009 Wolters Kluwer Health| Lippincott Williams & Wilkins.
ISSN: 17446880
Appears in Collections:Scopus 2006-2010

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