HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese

Pharmacogenomics. 2012 Jul;13(10):1193-201. doi: 10.2217/pgs.12.89.

Abstract

Aim: Allopurinol is widely used as an effective urate-lowering drug and is one of the most frequent causes of cutaneous adverse drug reactions (cADRs). Recently, a strong association of HLA-B*58:01 with allopurinol-induced severe cADRs was identified. This study investigated the predisposition to different types of allopurinol-cADRs conferred by HLA-B*5801 in a Han population from mainland China.

Patients & methods: HLA-B genotyping was performed on 38 Chinese patients with different types of allopurinol-cADRs from 2008 to 2011.

Results: All the allopurinol-cADR patients carried HLA-B*58:01, in contrast with only 11.11% (7/63) in the allopurinol-tolerant patients (odds ratio [OR] = 580.07; p < 0.0001) and 13.99% (80/572) in a Han Chinese population from the human MHC database (dbMHC; OR: 471.09; p < 0.0001) carried the genotype. Each type of allopurinol cADRs revealed a statistically significant association with HLA-B*58:01. In particular, the risk of allopurinol-induced maculopapular eruption was significantly higher in patients with HLA-B*58:01 (OR: 339.00; p < 0.0001).

Conclusion: The strong association of both the mild and severe types of allopurinol cADRs with the HLA-B*58:01 allele were observed. The results indicated that the prospective use of a genetic test of HLA-B*58:01 might reduce the prevalence of allopurinol-induced cADRs. Original submitted 7 March 2012; Revision submitted 21 May 2012.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Allopurinol* / administration & dosage
  • Allopurinol* / toxicity
  • China
  • Drug-Related Side Effects and Adverse Reactions / genetics
  • Exanthema / chemically induced
  • Exanthema / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-B Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Risk
  • Stevens-Johnson Syndrome / chemically induced
  • Stevens-Johnson Syndrome / genetics*

Substances

  • HLA-B Antigens
  • Allopurinol