TYK2 Promoter Variant and Diabetes Mellitus in the Japanese
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 loc...
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Elsevier
2015-07-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396415300128 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Seiho Nagafuchi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:52:04Z |
| format | Article |
| id | doaj.art-4513be54d16f42ffa11cc8aeca0b66f5 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-10T05:52:04Z |
| publishDate | 2015-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-4513be54d16f42ffa11cc8aeca0b66f52022-12-22T02:00:01ZengElsevierEBioMedicine2352-39642015-07-012774474910.1016/j.ebiom.2015.05.004TYK2 Promoter Variant and Diabetes Mellitus in the JapaneseSeiho Nagafuchi0Yumi Kamada-Hibio1Kanako Hirakawa2Nobutaka Tsutsu3Masae Minami4Akira Okada5Katsuya Kai6Miho Teshima7Arisa Moroishi8Yoshikazu Murakami9Yoshikazu Umeno10Yasushi Yokogawa11Kazuhiko Kogawa12Kenichi Izumi13Keizo Anzai14Ryuichi Iwakiri15Kazuyuki Hamaguchi16Nobuhiro Sasaki17Sakae Nohara18Eiko Yoshida19Mine Harada20Koichi Akashi21Toshihiko Yanase22Junko Ono23Toshimitsu Okeda24Ryoji Fujimoto25Kenji Ihara26Toshiro Hara27Yohei Kikuchi28Masanori Iwase29Takanari Kitazono30Fumiko Kojima31Suminori Kono32Hironori Kurisaki33Shiori Kondo34Hitoshi Katsuta35Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, JapanMinami Masae Naika Clinic, Fukuoka 815-0071, JapanOkada Naika Clinic, Fukuoka 812-0053, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanYamaguchi Red Cross Hospital, Yamaguchi 753-8519, JapanDepartment of Diabetes, Oita Red Cross Hospital, Oita 870-0033, JapanDepartment of Internal Medicine, Hamanomachi Hospital, Fukuoka 810-8539, JapanDepartment of Internal Medicine, Hamanomachi Hospital, Fukuoka 810-8539, JapanDepartmtent of Hepatology, Diabetes and Endocrinology, Saga University, Saga 849-8501, JapanDepartmtent of Hepatology, Diabetes and Endocrinology, Saga University, Saga 849-8501, JapanDepartment of Internal Medicine & Gastrointestinal Endoscopy, School of Medicine, Saga University, Saga 849-8501, JapanDepartment of Medicine, School of Medicine, Oita University, 849-8501, Oita 879-5593, JapanDepartment of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, JapanDepartment of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, JapanDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Clinical Laboratory Medicine, School of Medicine, Fukuoka University, Fukuoka 814-0180, JapanDepartment of Clinical Laboratory Medicine, School of Medicine, Fukuoka University, Fukuoka 814-0180, JapanDepartment of Internal Medicine, Shinkokura Hospital, Kitakyushu 803-8505, JapanDepartment of Internal Medicine, Shinkokura Hospital, Kitakyushu 803-8505, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanNational Institute of Health and Nutrition, Tokyo 162-8636, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanMatsuyama Red Cross Hospital, Matsuyama 790-8524, JapanDepartment of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanBackground: 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.http://www.sciencedirect.com/science/article/pii/S2352396415300128Tyrosine kinase 2 (TYK2)Promoter variantDiabetes mellitusVirusPolymorphism |
| spellingShingle | 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 TYK2 Promoter Variant and Diabetes Mellitus in the Japanese EBioMedicine Tyrosine kinase 2 (TYK2) Promoter variant Diabetes mellitus Virus Polymorphism |
| title | TYK2 Promoter Variant and Diabetes Mellitus in the Japanese |
| title_full | TYK2 Promoter Variant and Diabetes Mellitus in the Japanese |
| title_fullStr | TYK2 Promoter Variant and Diabetes Mellitus in the Japanese |
| title_full_unstemmed | TYK2 Promoter Variant and Diabetes Mellitus in the Japanese |
| title_short | TYK2 Promoter Variant and Diabetes Mellitus in the Japanese |
| title_sort | tyk2 promoter variant and diabetes mellitus in the japanese |
| topic | Tyrosine kinase 2 (TYK2) Promoter variant Diabetes mellitus Virus Polymorphism |
| url | http://www.sciencedirect.com/science/article/pii/S2352396415300128 |
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