title: 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 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 1,373 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-gamma 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.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. asmd@sc.itc.keio.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Motohashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamada
authors.forename: Taro
authors.initials: T
authors.lastname: Maruyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Susumu
authors.initials: S
authors.lastname: Kurihara
authors.forename: Miho
authors.initials: M
authors.lastname: Uga
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D044466:Asian People; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; D016753:Interleukin-10; D007371:Interferon-gamma