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Originally published In Press as doi:10.1167/iovs.07-1401 on February 8, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:1809-1813.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1401
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Association of Combined IL-13/IL-4R Signaling Pathway Gene Polymorphism with Stevens-Johnson Syndrome Accompanied by Ocular Surface Complications

Mayumi Ueta, Chie Sotozono, Tsutomu Inatomi, Kentaro Kojima, Junji Hamuro, and Shigeru Kinoshita

From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

PURPOSE. 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.






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