HLA class I and II gene polymorphisms in Stevens-Johnson syndrome with ocular complications in Japanese.
OBJECTIVE
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.
Ueta
Mayumi
M
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. mueta@ophth.kpu-m.ac.jp
Tokunaga
Katsushi
K
Sotozono
Chie
C
Inatomi
Tsutomu
T
Yabe
Toshio
T
Matsushita
Masaki
M
Mitsuishi
Yoko
Y
Kinoshita
Shigeru
S
D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D005128:Eye Diseases / Q000209:etiology*; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013262:Stevens-Johnson Syndrome / Q000150:complications* / Q000235:genetics*
D015234:HLA-A Antigens; C506470:HLA-A*01:01 antigen; C526286:HLA-A*02:06 antigen; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II