Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese

Abstract Type 1 diabetes is considered to be T-helper 1 (Th1) type autoimmune disease. Because the vitamin D receptor is expressed on CD4 + T cells and is known to affect cytokine responses, several groups have investigated the association between the vitamin D receptor gene BsmI polymorphism and ty...

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Published in:Journal of autoimmunity 2008-06, Vol.30 (4), p.207-211
Main Authors: Shimada, Akira, Kanazawa, Yasuhiko, Motohashi, Yoshiko, Yamada, Satoru, Maruyama, Taro, Ikegami, Hiroshi, Awata, Takuya, Kawasaki, Eiji, Kobayashi, Tetsuro, Nakanishi, Koji, Kawabata, Yumiko, Kurihara, Susumu, Uga, Miho, Tanaka, Shoichiro
Format: Article
Language:English
Subjects:
Allergy and Immunology
Asian Continental Ancestry Group
Biological and medical sciences
CD4-Positive T-Lymphocytes - immunology
Diabetes Mellitus, Type 1 - genetics
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Enzyme-Linked Immunosorbent Assay
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genetic Predisposition to Disease
Genotype
Humans
Interferon-gamma - biosynthesis
Interleukin-10 - biosynthesis
Male
Medical sciences
Polymerase Chain Reaction
Polymorphism, Genetic
Receptors, Calcitriol - genetics
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
T-helper 1 (Th1)
Type 1 diabetes
Vitamin D receptor
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Summary:Abstract Type 1 diabetes is considered to be T-helper 1 (Th1) type autoimmune disease. Because the vitamin D receptor is expressed on CD4 + T cells and is known to affect cytokine responses, several groups have investigated the association between the vitamin D receptor gene BsmI polymorphism and type 1 diabetes. However, this issue is still controversial; therefore, we examined this gene polymorphism in a large number of type 1 diabetic patients as a multi-center collaborative study in Japan. A total of 1373 subjects, including 774 cases and 599 control subjects of Japanese origin, were studied. The frequency of carriers of the BB genotype in type 1 diabetic patients was significantly higher than that in controls ( p < 0.01, odds ratio 3.65). Moreover, IFN-γ production upon anti-CD3 stimulation in the BB genotype group was significantly higher than that in the Bb and bb genotype groups ( p < 0.05), suggesting that the polyclonal T cell response in BB genotype patients is Th1 dominant. Based upon these results, we propose that it may be worthwhile to focus on subjects with the BB genotype of this gene polymorphism as having high risk for type 1 diabetes.
ISSN:0896-8411
1095-9157
DOI:10.1016/j.jaut.2007.09.002