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 - Funding Information:
The authors thank Itsuka Matsumoto, Ai Umei, Miki Kawano, Makoto Matsuo, Kiyoka Nishibayashi, Keiko Kajishima, and Dr. Morio Umeno at Sawara Hospital for their contribution in conducting this research. We acknowledge Angela Koh, Khoo Teck Puat Hospital, Singapore, and Dr. Chiri Nagatsuka for their help in the preparation of the manuscript. The authors also thank Drs. Aida Kaoru, Tetsuro Kobayashi, Nao Nishida and Takehiko Sasazuki for their helpful discussions. We also appreciate the technical support from the Research Support Center, Graduate School of Medical Sciences, Kyushu University. This work was supported by grants ( 19209037 and 21659230 ) from the Ministry of Education, Culture, Sports, Science and Technology and a grant (H22-Nanchi-097) from the Ministry of Health, Labor and Welfare of Japan . The funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.
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 -
