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 & 16 others 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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)744-749
Number of pages6
JournalEBioMedicine
Volume2
Issue number7
DOIs
Publication statusPublished - Jul 1 2015

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Medical problems
Type 1 Diabetes Mellitus
Diabetes Mellitus
Type 2 Diabetes Mellitus
Genes
TYK2 Kinase
Odds Ratio
Confidence Intervals
Viruses
Biomedical Technology
Glutamate Decarboxylase
Linkage Disequilibrium
Genetic Polymorphisms
Human Genome
Genetic Promoter Regions
Autoantibodies
Haplotypes
Sports
Exons
Japan

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nagafuchi, S., Kamada-Hibio, Y., Hirakawa, K., Tsutsu, N., Minami, M., Okada, A., ... Katsuta, H. (2015). TYK2 Promoter Variant and Diabetes Mellitus in the Japanese. EBioMedicine, 2(7), 744-749. https://doi.org/10.1016/j.ebiom.2015.05.004

TYK2 Promoter Variant and Diabetes Mellitus in the Japanese. / Nagafuchi, Seiho; Kamada-Hibio, Yumi; Hirakawa, Kanako; Tsutsu, Nobutaka; Minami, Masae; Okada, Akira; Kai, Katsuya; Teshima, Miho; Moroishi, Arisa; Murakami, Yoshikazu; Umeno, Yoshikazu; Yokogawa, Yasushi; Kogawa, Kazuhiko; Izumi, Kenichi; Anzai, Keizo; Iwakiri, Ryuichi; Hamaguchi, Kazuyuki; Sasaki, Nobuhiro; Nohara, Sakae; Yoshida, Eiko; Harada, Mine; Akashi, Koichi; Yanase, Toshihiko; Ono, Junko; Okeda, Toshimitsu; Fujimoto, Ryoji; Ihara, Kenji; Hara, Toshiro; Kikuchi, Yohei; Iwase, Masanori; Kitazono, Takanari; Kojima, Fumiko; Kono, Suminori; Kurisaki, Hironori; Kondo, Shiori; Katsuta, Hitoshi.

In: EBioMedicine, Vol. 2, No. 7, 01.07.2015, p. 744-749.

Research output: Contribution to journalArticle

Nagafuchi, S, Kamada-Hibio, Y, Hirakawa, K, Tsutsu, N, Minami, M, Okada, A, Kai, K, Teshima, M, Moroishi, A, Murakami, Y, Umeno, Y, Yokogawa, Y, Kogawa, K, Izumi, K, Anzai, K, Iwakiri, R, Hamaguchi, K, Sasaki, N, Nohara, S, Yoshida, E, Harada, M, Akashi, K, Yanase, T, Ono, J, Okeda, T, Fujimoto, R, Ihara, K, Hara, T, Kikuchi, Y, Iwase, M, Kitazono, T, Kojima, F, Kono, S, Kurisaki, H, Kondo, S & Katsuta, H 2015, 'TYK2 Promoter Variant and Diabetes Mellitus in the Japanese', EBioMedicine, vol. 2, no. 7, pp. 744-749. https://doi.org/10.1016/j.ebiom.2015.05.004
Nagafuchi S, Kamada-Hibio Y, Hirakawa K, Tsutsu N, Minami M, Okada A et al. TYK2 Promoter Variant and Diabetes Mellitus in the Japanese. EBioMedicine. 2015 Jul 1;2(7):744-749. https://doi.org/10.1016/j.ebiom.2015.05.004
Nagafuchi, Seiho ; Kamada-Hibio, Yumi ; Hirakawa, Kanako ; Tsutsu, Nobutaka ; Minami, Masae ; Okada, Akira ; Kai, Katsuya ; Teshima, Miho ; Moroishi, Arisa ; Murakami, Yoshikazu ; Umeno, Yoshikazu ; Yokogawa, Yasushi ; Kogawa, Kazuhiko ; Izumi, Kenichi ; Anzai, Keizo ; Iwakiri, Ryuichi ; Hamaguchi, Kazuyuki ; Sasaki, Nobuhiro ; Nohara, Sakae ; Yoshida, Eiko ; Harada, Mine ; Akashi, Koichi ; Yanase, Toshihiko ; Ono, Junko ; Okeda, Toshimitsu ; Fujimoto, Ryoji ; Ihara, Kenji ; Hara, Toshiro ; Kikuchi, Yohei ; Iwase, Masanori ; Kitazono, Takanari ; Kojima, Fumiko ; Kono, Suminori ; Kurisaki, Hironori ; Kondo, Shiori ; Katsuta, Hitoshi. / TYK2 Promoter Variant and Diabetes Mellitus in the Japanese. In: EBioMedicine. 2015 ; Vol. 2, No. 7. pp. 744-749.
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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.",
author = "Seiho Nagafuchi and Yumi Kamada-Hibio and Kanako Hirakawa and Nobutaka Tsutsu and Masae Minami and Akira Okada and Katsuya Kai and Miho Teshima and Arisa Moroishi and Yoshikazu Murakami and Yoshikazu Umeno and Yasushi Yokogawa and Kazuhiko Kogawa and Kenichi Izumi and Keizo Anzai and Ryuichi Iwakiri and Kazuyuki Hamaguchi and Nobuhiro Sasaki and Sakae Nohara and Eiko Yoshida and Mine Harada and Koichi Akashi and Toshihiko Yanase and Junko Ono and Toshimitsu Okeda and Ryoji Fujimoto and Kenji Ihara and Toshiro Hara and Yohei Kikuchi and Masanori Iwase and Takanari Kitazono and Fumiko Kojima and Suminori Kono and Hironori Kurisaki and Shiori Kondo and Hitoshi Katsuta",
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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

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.

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