HLA class I and II gene polymorphisms in Stevens-Johnson syndrome with ocular complications in Japanese

Mol Vis. 2008 Mar 17;14:550-5.

Abstract

Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents and/or inciting drugs. Although the pathobiological mechanisms underlying the onset of SJS/TEN have not been fully established, the extreme rarity of cutaneous and ocular surface reactions to drug therapies led us to suspect individual susceptibility. Our previous study of polymorphisms in the HLA-class I genes of 40 Japanese SJS/TEN patients with ocular surface complications showed that in the Japanese, HLA-A*0206 was strongly associated with SJS/TEN. In this study, we investigated the association between HLA class II antigens in addition to HLA class I antigens and SJS/TEN.

Methods: We studied the histocompatibility antigen genes, HLA-A, B, C, DRB1, and DQB1, of 71 Japanese SJS/TEN patients with ocular complications. We also genotyped 113 healthy volunteers for HLA-A, B, C, DRB1, and DQB1. We performed polymerase chain reaction amplification followed by hybridization with sequence-specific oligonucleotide probes (PCR-SSO) using commercial bead-based typing kits.

Results: HLA-A*0206 was strongly associated with SJS/TEN. HLA-A*1101 was inversely associated. HLA-B*5901 exhibited a high odds ratio for SJS/TEN with ocular complications. However, when we corrected the p-value for the number of alleles detected (n=29), the results ceased to be significant. There was no association between HLA-C and SJS/TEN. There was also no significant association between HLA-DRB1 and SJS/TEN. HLA-DQB1*0502 was negatively and weakly associated with SJS/TEN although correction of the p-value for the number of alleles detected rendered the result not significant.

Conclusions: Because our findings are completely different from data reported on Caucasian patients, they suggest strong ethnic differences in the HLA-SJS associations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Asians / genetics*
  • Eye Diseases / etiology*
  • Female
  • HLA-A Antigens / genetics
  • HLA-A1 Antigen
  • HLA-A2 Antigen
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Male
  • Middle Aged
  • Stevens-Johnson Syndrome / complications*
  • Stevens-Johnson Syndrome / genetics*

Substances

  • HLA-A Antigens
  • HLA-A*01:01 antigen
  • HLA-A*02:06 antigen
  • HLA-A1 Antigen
  • HLA-A2 Antigen
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II