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This version published online on October 13, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-0931
A more recent version of this article appeared on January 1, 2005
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Submitted on May 17, 2004
Accepted on October 1, 2004

Interleukin-13 gene polymorphisms confer the susceptibility of Japanese populations to Graves' disease

Yuji Hiromatsu*, Tomoka Fukutani, Michiko Ichimura, Tokunori Mukai, Hiroo Kaku, Hitomi Nakayama, Ikuyo Miyake, Shingo Shoji, Yoshiro Koda, and Tomasz Bednarkzuk

Department of Endocrinology and Metabolism, and the Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan, Department of Endocrinology, Medical Research Center, Polish Academy of Science, Warsaw, Poland

* To whom correspondence should be addressed.
Yuji Hiromatsu, E-mail: yuji{at}med.kurume-u.ac.jp

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. Interleukin 13 (IL-13) is an important mediator of anti-inflammatory 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 anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 244). A C/T polymorphism at position -1,112 of the promoter region was measured using the direct sequencing method, and an Arg130Gln (G2,044A) polymorphism in exon 4 was examined using the PCR-restriction fragment length polymorphism method. There was a significant decrease in the -1,112T allele frequency in the GD patients compared with the controls (16% vs. 23%, P = 0.0019). The frequency of the 2,044A allele on exon 4 also appeared lower in the GD patients compared with the controls. Haplotype analysis showed a significant decrease of the -1,112T/2,044A haplotype in the GD patients. There was no association between the IL-13 gene polymorphisms and ophthalmopathy, severity or serum IgE levels. In conclusion, IL-13 gene polymorphisms are associated with GD susceptibility in Japan.
Key words: Polymorphism • IL-13 • IgE • Graves' disease • Graves' ophthalmopathy




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