Association of combined IL-13/IL-4R signaling pathway gene polymorphism with Stevens-Johnson syndrome with ocular surface complications
Mayumi Ueta 1*,
Chie Sotozono 2,
Tsutomu Inatomi 1,
Kentaro Kojima 1,
Junji Hamuro 1,
and
Shigeru Kinoshita 1
1 Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
2 Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto , Japan
* To whom correspondence should be addressed. E-mail: mueta{at}ophth.kpu-m.ac.jp.
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Abstract |
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Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents and/or inciting drugs. We previously reported that there is an association between SJS/TEN and IL-4R gene polymorphism which is essential for both 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, we performed polymorphism analysis. Methods: In 76 Japanese SJS/TEN patients with ocular surface complications and 160 healthy controls, we 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. As 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. Our 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.
Key Words:
Stevens-Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN), ocular surface complications, single nucleotide polymorphism (SNP), IL-4R, IL-13
