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 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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
Ministry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan.
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan ; Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan ; Department of Internal Medicine, Sawara Hospital, Sawara, Fukuoka 819-0002, Japan.
Seiho
S
Nagafuchi
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yumi
Y
Kamada-Hibio
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Kanako
K
Hirakawa
Department of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, Japan.
Nobutaka
N
Tsutsu
Minami Masae Naika Clinic, Fukuoka 815-0071, Japan.
Masae
M
Minami
Okada Naika Clinic, Fukuoka 812-0053, Japan.
Akira
A
Okada
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Katsuya
K
Kai
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Miho
M
Teshima
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Arisa
A
Moroishi
Yamaguchi Red Cross Hospital, Yamaguchi 753-8519, Japan.
Yoshikazu
Y
Murakami
Department of Diabetes, Oita Red Cross Hospital, Oita 870-0033, Japan.
Yoshikazu
Y
Umeno
Department of Internal Medicine, Hamanomachi Hospital, Fukuoka 810-8539, Japan.
Yasushi
Y
Yokogawa
Department of Internal Medicine, Hamanomachi Hospital, Fukuoka 810-8539, Japan.
Kazuhiko
K
Kogawa
Departmtent of Hepatology, Diabetes and Endocrinology, Saga University, Saga 849-8501, Japan.
Kenichi
K
Izumi
Departmtent of Hepatology, Diabetes and Endocrinology, Saga University, Saga 849-8501, Japan.
Keizo
K
Anzai
Department of Internal Medicine & Gastrointestinal Endoscopy, School of Medicine, Saga University, Saga 849-8501, Japan.
Ryuichi
R
Iwakiri
Department of Medicine, School of Medicine, Oita University, 849-8501, Oita 879-5593, Japan.
Kazuyuki
K
Hamaguchi
Department of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, Japan.
Nobuhiro
N
Sasaki
Department of Diabetes and Metabolism, Fukuoka Red Cross Hospital, Fukuoka 815-8555, Japan.
Sakae
S
Nohara
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Eiko
E
Yoshida
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Mine
M
Harada
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Koichi
K
Akashi
Department of Clinical Laboratory Medicine, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan ; Department of Diabetology and Metabolism, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
Toshihiko
T
Yanase
Department of Clinical Laboratory Medicine, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan ; Department of Diabetology and Metabolism, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
Junko
J
Ono
Department of Internal Medicine, Shinkokura Hospital, Kitakyushu 803-8505, Japan.
Toshimitsu
T
Okeda
Department of Internal Medicine, Shinkokura Hospital, Kitakyushu 803-8505, Japan.
Ryoji
R
Fujimoto
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Kenji
K
Ihara
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Toshiro
T
Hara
Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yohei
Y
Kikuchi
Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Masanori
M
Iwase
Department of Medicine and Clinical Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Takanari
T
Kitazono
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Fumiko
F
Kojima
National Institute of Health and Nutrition, Tokyo 162-8636, Japan.
Suminori
S
Kono
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Hironori
H
Kurisaki
Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan.
Shiori
S
Kondo
Department of Medical Science and Technology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan ; Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan ; Department of Internal Medicine, Sawara Hospital, Sawara, Fukuoka 819-0002, Japan.
Hitoshi
H
Katsuta
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053634:TYK2 Kinase / Q000235:genetics*; D055815:Young Adult
D053634:TYK2 Kinase
Diabetes mellitus; Polymorphism; Promoter variant; Tyrosine kinase 2 (TYK2); Virus