TY - JOUR
T1 - TYK2 Promoter Variant and Diabetes Mellitus in the Japanese
AU - Nagafuchi, Seiho
AU - Kamada-Hibio, Yumi
AU - Hirakawa, Kanako
AU - Tsutsu, Nobutaka
AU - Minami, Masae
AU - Okada, Akira
AU - Kai, Katsuya
AU - Teshima, Miho
AU - Moroishi, Arisa
AU - Murakami, Yoshikazu
AU - Umeno, Yoshikazu
AU - Yokogawa, Yasushi
AU - Kogawa, Kazuhiko
AU - Izumi, Kenichi
AU - Anzai, Keizo
AU - Iwakiri, Ryuichi
AU - Hamaguchi, Kazuyuki
AU - Sasaki, Nobuhiro
AU - Nohara, Sakae
AU - Yoshida, Eiko
AU - Harada, Mine
AU - Akashi, Koichi
AU - Yanase, Toshihiko
AU - Ono, Junko
AU - Okeda, Toshimitsu
AU - Fujimoto, Ryoji
AU - Ihara, Kenji
AU - Hara, Toshiro
AU - Kikuchi, Yohei
AU - Iwase, Masanori
AU - Kitazono, Takanari
AU - Kojima, Fumiko
AU - Kono, Suminori
AU - Kurisaki, Hironori
AU - Kondo, Shiori
AU - Katsuta, Hitoshi
N1 - Publisher Copyright:
© 2015.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Background: Recently, natural mutation of Tyrosine kinase 2 (Tyk2) gene has been shown to determine susceptibility to murine virus-induced diabetes. In addition, a previous human genome-wide study suggested the type 1 diabetes (T1D) susceptibility region to be 19p13, where the human TYK2 gene is located (19p13.2). Methods: Polymorphisms of TYK2 gene at the promoter region and exons were studied among 331 healthy controls, and 302 patients with T1D and 314 with type 2 diabetes (T2D) in the Japanese. Findings: A TYK2 promoter haplotype with multiple genetic polymorphisms, which are in complete linkage disequilibrium, named TYK2 promoter variant, presenting decreased promoter activity, is associated with an increased risk of not only T1D (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.6; P=. 0.01), but also T2D (OR, 2.1; 95% CI, 1.1 to 4.1; P=. 0.03). The risk is high in patients with T1D associated with flu-like syndrome at diabetes onset and also those without anti-glutamic acid decarboxylase autoantibody. Interpretation: The TYK2 promoter variant is associated with an overall risk for diabetes, serving a good candidate as a virus-induced diabetes susceptibility gene in humans. Funding: Ministry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan.
AB - Background: Recently, natural mutation of Tyrosine kinase 2 (Tyk2) gene has been shown to determine susceptibility to murine virus-induced diabetes. In addition, a previous human genome-wide study suggested the type 1 diabetes (T1D) susceptibility region to be 19p13, where the human TYK2 gene is located (19p13.2). Methods: Polymorphisms of TYK2 gene at the promoter region and exons were studied among 331 healthy controls, and 302 patients with T1D and 314 with type 2 diabetes (T2D) in the Japanese. Findings: A TYK2 promoter haplotype with multiple genetic polymorphisms, which are in complete linkage disequilibrium, named TYK2 promoter variant, presenting decreased promoter activity, is associated with an increased risk of not only T1D (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.6; P=. 0.01), but also T2D (OR, 2.1; 95% CI, 1.1 to 4.1; P=. 0.03). The risk is high in patients with T1D associated with flu-like syndrome at diabetes onset and also those without anti-glutamic acid decarboxylase autoantibody. Interpretation: The TYK2 promoter variant is associated with an overall risk for diabetes, serving a good candidate as a virus-induced diabetes susceptibility gene in humans. Funding: Ministry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan.
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U2 - 10.1016/j.ebiom.2015.05.004
DO - 10.1016/j.ebiom.2015.05.004
M3 - Article
C2 - 26288847
AN - SCOPUS:84951573859
SN - 2352-3964
VL - 2
SP - 744
EP - 749
JO - EBioMedicine
JF - EBioMedicine
IS - 7
ER -
