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Interleukin-13 Gene Polymorphisms Confer the Susceptibility of Japanese Populations to Graves’ Disease

Department of Endocrinology and Metabolism (Y.H., T.F., M.I., T.M., H.K., H.N., I.M., S.S.) and Division of Human Genetics, Department of Forensic Medicine (Y.K.), Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan; and Department of Endocrinology, Medical Research Center, Polish Academy of Science (T.B.), Warsaw, Poland 02-097

Address all correspondence and requests for reprints to: Dr. Yuji Hiromatsu, Department of Endocrinology and Metabolism, Kurume University School of Medicine, 67 Asahimatchi, Kurume, Fukuoka 830-0011, Japan. E-mail: yuji{at}med.kurume-u.ac.jp.

Graves’ disease (GD) is an autoimmune disorder with genetic predisposition. IL-13 is an important mediator of antiinflammatory immune responses and is expressed in the thyroid and orbit. The aim of the present study was to investigate whether IL-13 gene polymorphisms are associated with the development of GD. IL-13 gene polymorphisms were studied in Japanese GD patients (n = 310) and healthy control subjects without antithyroid autoantibodies or a family history of autoimmune disorders (n = 244). A C/T polymorphism at position –1112 of the promoter region was measured using the direct sequencing method, and an Arg¹³⁰Gln (G2044A) polymorphism in exon 4 was examined using the PCR-restriction fragment length polymorphism method. There was a significant decrease in –1112T allele frequency in GD patients compared with controls (16% vs. 23%; P = 0.0019). The frequency of the 2044A allele on exon 4 also appeared lower in GD patients compared with controls. Haplotype analysis showed a significant decrease in the –1112T/2044A haplotype in GD patients. There was no association between IL-13 gene polymorphisms and ophthalmopathy, severity, or serum IgE levels. In conclusion, IL-13 gene polymorphisms are associated with GD susceptibility in Japan.

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