Association of combined IL-13/IL-4R signaling pathway gene polymorphism with Stevens-Johnson syndrome accompanied by ocular surface complications.
OBJECTIVE
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents or inciting drugs. The authors previously reported an association between SJS/TEN and IL-4R gene polymorphism that is essential for IL-4 and IL-13 signaling. To examine IL-4 and IL-13 gene polymorphisms and the combination of these polymorphisms with IL-4R polymorphism, the authors performed polymorphism analysis.


METHODS
In 76 Japanese SJS/TEN patients with ocular surface complications and 160 healthy controls, the authors analyzed polymorphisms of the promoter -590C/T in the IL-4 gene and of the promoter -1111C/T and Arg110Gln in the IL-13 gene and assessed Gln551Arg in the IL-4R gene. Because Arg110Gln affects serum IL-13, plasma IL-13 levels were also examined.


RESULTS
In the SJS/TEN patients, the Arg110Gln SNP of IL-13 was significantly associated with the disease, and the frequency of Arg110 alleles was significantly higher than that in the controls. Plasma IL-13 tended to be lower in SJS/TEN patients than in the controls. Analysis of the genotype pattern of IL-4R SNP Gln551Arg and IL-13 SNP Arg110Gln showed that the Gln551Gln(A/A)-Arg110Arg(G/G) genotype pattern was also associated with SJS/TEN.


CONCLUSIONS
IL-13 gene polymorphisms might be associated with SJS/TEN with ocular surface complications. The present findings suggest that SJS/TEN is different from allergic diseases such as atopy and asthma because the ratio of each allele in the IL-13 SNP Arg110Gln was the opposite of the ratio in those diseases. They also reveal that combined polymorphisms in the IL-13/IL-4R signaling pathway were associated with SJS/TEN with ocular surface complications.
Ueta
Mayumi
M
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Hirokoji, Kawaramachi, Kamigyoku, Kyoto, Japan. mueta@ophth.kpu-m.ac.jp
Sotozono
Chie
C
Inatomi
Tsutomu
T
Kojima
Kentaro
K
Hamuro
Junji
J
Kinoshita
Shigeru
S
D000328:Adult; D016022:Case-Control Studies; D003231:Conjunctivitis / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000097:blood / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013262:Stevens-Johnson Syndrome / Q000097:blood / Q000235:genetics*
D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4