Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population

Basic Clin Pharmacol Toxicol. 2011 Jul;109(1):42-6. doi: 10.1111/j.1742-7843.2011.00681.x. Epub 2011 Mar 16.

Abstract

Lamotrigine (LTG) is a commonly used antiepileptic drug. However, the use of LTG is limited because of its cutaneous adverse drug reactions (cADRs) ranging from mild maculopapular eruption (MPE) to severe Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between HLA-B*1502 and carbamazepine-induced SJS/TEN has been identified in Chinese and Thai. Although three of seven cases with HLA-B*1502 have been reported in LTG-induced SJS/TEN so far, the relationship between HLA-B*1502 and LTG-induced SJS/TEN needs further investigation. It is also unclear whether there is a specific genetic marker associated with LTG-induced MPE in Chinese. In this study, we genotyped 43 Han Chinese patients treated with LTG (14 cases with LTG-induced cADRs and 29 LTG-tolerant controls), using PCR-SSP for HLA-B*1502 testing and low-resolution genotyping, as well as sequencing for four-digit genotyping. The two cases with SJS were negative for HLA-B*1502, with B1301/1301 and 4601/5610, respectively. Combining the data with previous studies, there was no significant difference in the frequency of subjects with HLA-B*1502 between the LTG-induced SJS/TEN group and the LTG-tolerant group (p = 0.08, OR 4.23, 95% CI 0.94-18.97). In the MPE group, only one was positive for HLA-B*1502. There was no significant difference in the frequency of a specific HLA-B allele between the MPE group and the LTG-tolerant group either. In this study, no significant association between HLA-B*1502 and LTG-induced SJS or MPE was found. Given the small sample size and only HLA-B locus genotyping, further large-scale studies are required to explore genetic associations with LTG-induced cADRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Alleles
  • Anticonvulsants / adverse effects*
  • Asian People / genetics
  • Base Sequence
  • Child
  • Child, Preschool
  • China
  • DNA Primers
  • Drug Eruptions / etiology*
  • Drug Eruptions / genetics
  • Female
  • Gene Frequency
  • Genotype
  • HLA-B Antigens / genetics*
  • Humans
  • Lamotrigine
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Triazines / adverse effects*
  • Young Adult

Substances

  • Anticonvulsants
  • DNA Primers
  • HLA-B Antigens
  • Triazines
  • Lamotrigine