TYK2 Promoter Variant and Diabetes Mellitus in the Japanese.
TYK2 Promoter Variant and Diabetes Mellitus in the Japanese.
复制标题
DOI：
10.1016/j.ebiom.2015.05.004
复制
发表时间：
2015-07
期刊：
影响因子：
11.1
通讯作者：
Katsuta H
中科院分区：
文献类型：
--
作者：
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
最近，酪氨酸激酶2 （Tyk2）基因的自然突变已被证明与小鼠病毒诱导的糖尿病易感性有关。此外，先前的一项人类全基因组研究表明，1型糖尿病（T1D）的易感区域为19p13，人类TYK2基因位于该区域（19p13.2）。研究了日本331名健康对照、302名T1D患者和314名2型糖尿病（T2D）患者启动子区和外显子TYK2基因多态性。具有多种遗传多态性的TYK2启动子单倍型，处于完全的连锁不平衡状态，被称为TYK2启动子变异，表现为启动子活性降低，不仅与T1D的风险增加有关(比值比（OR）， 2.4；95%置信区间（CI）， 1.2 ~ 4.6；P = 0.01),但也T2D(优势比,2.1;95%置信区间,1.1至4.1;P = 0.03)。糖尿病发病时与流感样综合征相关的T1D患者以及无抗谷氨酸脱羧酶自身抗体的患者的风险较高。TYK2启动子变异与糖尿病的总体风险相关，是人类病毒诱导的糖尿病易感基因的良好候选基因。日本教育、文化、体育、科学和技术部以及卫生、劳动和福利部。在日本人中发现了具有多重多态性的TYK2启动子变异。TYK2启动子变异与1型和2型糖尿病的风险增加有关。TYK2启动子变异是病毒诱导的人类糖尿病易感基因的一个很好的候选基因。
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). 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. 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. 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. Ministry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan. TYK2 promoter variant with multiple polymorphisms was identified in the Japanese. TYK2 promoter variant is associated with an increased risk of both type 1 and type 2 diabetes. TYK2 promoter variant serves a good candidate as a virus-induced diabetes susceptibility gene in humans.