EBioMedicine (Jul 2015)
TYK2 Promoter Variant and Diabetes Mellitus in the Japanese
- Seiho Nagafuchi,
- Yumi Kamada-Hibio,
- Kanako Hirakawa,
- Nobutaka Tsutsu,
- Masae Minami,
- Akira Okada,
- Katsuya Kai,
- Miho Teshima,
- Arisa Moroishi,
- Yoshikazu Murakami,
- Yoshikazu Umeno,
- Yasushi Yokogawa,
- Kazuhiko Kogawa,
- Kenichi Izumi,
- Keizo Anzai,
- Ryuichi Iwakiri,
- Kazuyuki Hamaguchi,
- Nobuhiro Sasaki,
- Sakae Nohara,
- Eiko Yoshida,
- Mine Harada,
- Koichi Akashi,
- Toshihiko Yanase,
- Junko Ono,
- Toshimitsu Okeda,
- Ryoji Fujimoto,
- Kenji Ihara,
- Toshiro Hara,
- Yohei Kikuchi,
- Masanori Iwase,
- Takanari Kitazono,
- Fumiko Kojima,
- Suminori Kono,
- Hironori Kurisaki,
- Shiori Kondo,
- Hitoshi Katsuta
Affiliations
- Seiho Nagafuchi
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Yumi Kamada-Hibio
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Kanako Hirakawa
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Nobutaka Tsutsu
- Department of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, Japan
- Masae Minami
- Minami Masae Naika Clinic, Fukuoka 815-0071, Japan
- Akira Okada
- Okada Naika Clinic, Fukuoka 812-0053, Japan
- Katsuya Kai
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Miho Teshima
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Arisa Moroishi
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Yoshikazu Murakami
- Yamaguchi Red Cross Hospital, Yamaguchi 753-8519, Japan
- Yoshikazu Umeno
- Department of Diabetes, Oita Red Cross Hospital, Oita 870-0033, Japan
- Yasushi Yokogawa
- Department of Internal Medicine, Hamanomachi Hospital, Fukuoka 810-8539, Japan
- Kazuhiko Kogawa
- Department of Internal Medicine, Hamanomachi Hospital, Fukuoka 810-8539, Japan
- Kenichi Izumi
- Departmtent of Hepatology, Diabetes and Endocrinology, Saga University, Saga 849-8501, Japan
- Keizo Anzai
- Departmtent of Hepatology, Diabetes and Endocrinology, Saga University, Saga 849-8501, Japan
- Ryuichi Iwakiri
- Department of Internal Medicine & Gastrointestinal Endoscopy, School of Medicine, Saga University, Saga 849-8501, Japan
- Kazuyuki Hamaguchi
- Department of Medicine, School of Medicine, Oita University, 849-8501, Oita 879-5593, Japan
- Nobuhiro Sasaki
- Department of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, Japan
- Sakae Nohara
- Department of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, Japan
- Eiko Yoshida
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Mine Harada
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Koichi Akashi
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Toshihiko Yanase
- Department of Clinical Laboratory Medicine, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan
- Junko Ono
- Department of Clinical Laboratory Medicine, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan
- Toshimitsu Okeda
- Department of Internal Medicine, Shinkokura Hospital, Kitakyushu 803-8505, Japan
- Ryoji Fujimoto
- Department of Internal Medicine, Shinkokura Hospital, Kitakyushu 803-8505, Japan
- Kenji Ihara
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Toshiro Hara
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Yohei Kikuchi
- Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Masanori Iwase
- Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Takanari Kitazono
- Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Fumiko Kojima
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Suminori Kono
- National Institute of Health and Nutrition, Tokyo 162-8636, Japan
- Hironori Kurisaki
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Shiori Kondo
- Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan
- Hitoshi Katsuta
- Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- DOI
- https://doi.org/10.1016/j.ebiom.2015.05.004
- Journal volume & issue
-
Vol. 2,
no. 7
pp. 744 – 749
Abstract
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.
Keywords
