title: HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients.
abstract: OBJECTIVE
  Investigation of a possible involvement of differences in human leukocyte antigens (HLA) in the risk of nevirapine (NVP)-induced 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 (CI)=4.87-73.44, Pc=4.6x10] and 0.7% in general Thai population (OR=29.87; 95% CI=5.04-175.86, Pc=2.6x10). The logistic regression analysis also indicated HLA-B*3505 to be significantly associated with skin rash with OR of 49.15 (95% CI=6.45-374.41, P=0.00017).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Group for Pharmacogenomics, RIKEN, Center for Genomic Medicine, Tokyo, Japan.
authors.forename: Soranun
authors.initials: S
authors.lastname: Chantarangsu
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
authors.forename: Sasisopin
authors.initials: S
authors.lastname: Kiertiburanakul
authors.forename: Somnuek
authors.initials: S
authors.lastname: Sungkanuparph
authors.forename: Weerawat
authors.initials: W
authors.lastname: Manosuthi
authors.forename: Woraphot
authors.initials: W
authors.lastname: Tantisiriwat
authors.forename: Angkana
authors.initials: A
authors.lastname: Charoenyingwattana
authors.forename: Thanyachai
authors.initials: T
authors.lastname: Sura
authors.forename: Wasun
authors.initials: W
authors.lastname: Chantratita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D005076:Exanthema / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D013785:Thailand
chemical_list: D019380:Anti-HIV Agents; D015235:HLA-B Antigens; D019829:Nevirapine