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Vitamin D Receptor Gene Polymorphism Affects Onset Pattern of Type 1 Diabetes

Department of Internal Medicine (Y.M., S.Y., R.S., H.H., A.S., T.S.), Keio University School of Medicine, Tokyo 160-8582; Department of Internal Medicine (T.Y.), Nerima General Hospital, Tokyo 176-8583; Department of Internal Medicine (T.M.), Saitama Social Insurance Hospital, Saitama 336-0002; Department of Neurology (M.N.), Hokkaido University Graduate School of Medicine, Sapporo 060-8638; Hokuyukai Neurology Hospital (T.F.), Sapporo 063-0802; Department of Internal Medicine (A.K.), Tokyo Denryoku Hospital, Tokyo 160-0016; and Chugai Diagnostic Science Research Center (K.M.), Tokyo 104-8301, Japan

Address all correspondence and requests for reprints to: Yoshiko Motohashi, M.D., 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: asmd{at}sc.itc.keio.ac.jp.

Type 1 diabetes mellitus is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to the vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. We, therefore, investigated a VDR gene polymorphism in type 1 diabetes. We examined the VDR gene Bsm I polymorphism in 203 type 1 diabetic patients and 222 controls, and the association between the VDR gene polymorphism and type 1 diabetes and their onset pattern. We found a significantly higher frequency of B allele in type 1 diabetics overall, compared with controls (P = 0.0010). Moreover, there was a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls (P = 0.0002), whereas this difference was not observed between slow-onset type 1 diabetics and controls. Regardless of the existence of islet-associated autoantibody, we found a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls. In conclusion, we found an association between a VDR gene polymorphism and acute-onset type 1 diabetes. Assessment of this VDR gene polymorphism may contribute to prediction of the onset pattern in individuals with a high risk of type 1 diabetes.

Y.M. and S.Y. contributed equally to this work.

Abbreviations: GADA, anti-GAD65 antibody; HLA, human lymphocyte antigen(s); IAA, insulin autoantibody; NOD, non-obese diabetic; 1,25(OH)₂ D₃, 1,25-dihydroxy vitamin D3; Th, T-helper; VDR, vitamin D receptor.

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