Association between HLA-B*58:01 allele and severe cutaneous adverse reactions with allopurinol in Han Chinese in Hong Kong

Br J Dermatol. 2012 Jul;167(1):44-9. doi: 10.1111/j.1365-2133.2012.10894.x. Epub 2012 May 8.

Abstract

Background: Allopurinol has been reported as a common cause of severe cutaneous adverse reactions (SCARs). Recent studies in various populations suggest that HLA-B*58:01 is a strong genetic marker for allopurinol-induced SCAR, especially in populations with a high frequency of HLA-B*58:01.

Objectives: To confirm the association link between HLA-B*58:01 and hypersensitivity reactions attributed to allopurinol use in Han Chinese patients in Hong Kong.

Methods: We performed a case-control study to investigate whether the HLA-B*58:01 allele predisposes to allopurinol-induced SCAR in Han Chinese patients in Hong Kong. The HLA-B*58:01 genotyping was performed in 20 patients with allopurinol-induced SCAR or erythema multiforme major (EMM; n = 1) and in 30 patients tolerant to allopurinol.

Results: All of the 19 patients with allopurinol-induced SCAR examined but not the patient with EMM carried HLA-B*58:01 whereas only four (13%) of the control patients had this allele. The positive rate of the HLA-B*58:01 was significantly higher in the cases than in the allopurinol-tolerant control group [odds ratio (OR) 123·5, 95% confidence interval (CI) 12·8-1195·1; P < 1 × 10(-4) ] and was even higher after removal of the patient with EMM (OR 229·7, 95% CI 11·7-4520·4). The sensitivity and specificity of the HLA-B*58:01 allele for prediction of allopurinol-induced SCAR were 100% and 86·7%, respectively.

Conclusions: This study confirmed the strong association between the HLA-B*58:01 and allopurinol-induced SCAR in Hong Kong Han Chinese patients. A screening test for the HLA-B*58:01 allele should effectively reduce the risk for allopurinol-induced SCAR in Chinese populations.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Allopurinol / adverse effects*
  • Asians / ethnology
  • Case-Control Studies
  • Drug Eruptions / ethnology
  • Drug Eruptions / genetics*
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • HLA-B Antigens / genetics*
  • Hong Kong / ethnology
  • Humans
  • Male
  • Middle Aged
  • Uricosuric Agents / therapeutic use*

Substances

  • HLA-B Antigens
  • Uricosuric Agents
  • Allopurinol