Stromal-cell derived factor-1 chemokine gene variant is associated with type 1 diabetes age at onset in Japanese population |
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Authors: | Ide Akane Kawasaki Eiji Abiru Norio Sun Fuyan Fukushima Tetsuya Takahashi Ryoko Kuwahara Hironaga Fujita Naruhiro Kita Atsushi Oshima Katsuya Uotani Shigeo Yamasaki Hironori Yamaguchi Yoshihiko Kawabata Yumiko Fujisawa Tomomi Ikegami Hiroshi Eguchi Katsumi |
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Affiliation: | First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. |
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Abstract: | Stromal-cell derived factor-1 (SDF-1) is a powerful chemokine that upregulates T-cell migration and activation. The gene for SDF-1 is located near type 1 diabetes susceptibility locus IDDM10, suggesting a contribution by SDF-1 to the induction of diabetes. Recently the role of SDF-1 gene polymorphism in the clinical presentation of type 1 diabetes in French population has been reported. To test the putative involvement of SDF-1 gene polymorphism in predisposition to or clinical heterogeneity of type 1 diabetes in Japanese population, we conducted the case-control study. The SDF1-3'A variant (801 G to A in the 3'-untranslated region) was determined by the polymerase chain reaction-restriction fragment length polymorphism technique in 184 patients with abrupt-onset type 1 diabetes and 106 healthy control subjects. No significant difference in allele and genotype frequencies of SDF1-3'A variant was found between type 1 diabetic patients and healthy controls. However, the SDF1-3'A variant was strongly associated with early-onset diabetes in a recessive model (AA versus AG + GG, p = 0.017). The mean age-at-onset in patients carrying SDF1-3'AA genotype was significantly younger than that in patients with SDF1-3' AG or GG genotype (p = 0.028). The frequencies of SDF1-3' A variant were significantly increased in HLA-DR4/9 patients compared with non-DR4/9 patients (p = 0.008). These results suggest that the SDF-1 gene polymorphism is associated with the age-at-onset of type 1 diabetes in Japanese population. |
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