TYK2 Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients.
TYK2 Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients.
复制标题
DOI：
10.3390/genes12030400
复制
发表时间：
2021-03-11
期刊：
影响因子：
3.5
通讯作者：
Anzai K
中科院分区：
文献类型：
--
作者：
Mori H;Takahashi H;Mine K;Higashimoto K;Inoue K;Kojima M;Kuroki S;Eguchi T;Ono Y;Inuzuka S;Soejima H;Nagafuchi S;Anzai K
越来越多的证据表明，病毒感染导致1型糖尿病是由于直接β细胞损伤和触发对β细胞的自身免疫反应性。在这里，我们阐明了酪氨酸激酶2（Tyk 2）基因，编码干扰素受体信号分子，是负责病毒诱导的糖尿病小鼠，其启动子变体赋予1型糖尿病的风险在人类。本研究探讨了TYK 2启动子变异体（TYK 2 PV）与2型糖尿病患者胰岛素分泌的关系。在未使用磺酰脲类药物或胰岛素药物的2型糖尿病患者中，使用直接DNA测序确定TYK 2 PV状态，并评估其与空腹胰岛素、C肽和胰岛素抵抗稳态模型评估（HOMA-IR）的相关性。在评估的172例患者中，18例（10.5%）显示TYK 2 PV阳性。他们的体重指数（BMI）显著低于没有变异的人（23.4 vs. 25.4 kg/m2，p = 0.025）。有变异的患者空腹胰岛素（3.9 vs. 6.2 μIU/mL，p = 0.007）、C肽（1.37 vs. 1.76 ng/mL，p = 0.008）和HOMA-IR（1.39 vs. 2.05，p = 0.006）低于无变异的患者。多变量分析发现TYK 2 PV与空腹胰岛素≤ 5 μIU/mL（比值比（OR）3.63，p = 0.025）和C肽≤ 1.0 ng/mL（OR 3.61，p = 0.028）相关，还与较低的胰岛素抵抗（HOMA-IR ≤ 2.5; OR 8.60，p = 0.042）相关。TYK 2 PV与2型糖尿病中胰岛素分泌受损和低胰岛素抵抗相关。TYK 2 PV的2型糖尿病患者应仔细随访，以便接受适当的治疗，包括胰岛素注射。
Accumulating evidence has suggested that viral infection causes type 1 diabetes due to direct β-cell damage and the triggering of autoimmune reactivity to β cells. Here, we elucidated that the tyrosine kinase 2 (Tyk2) gene, encoding an interferon receptor signaling molecule, is responsible for virus-induced diabetes in mice, and its promoter variant confers a risk of type 1 diabetes in humans. This study investigated the relationship between a TYK2 promoter variant (TYK2PV) and insulin secretion in type 2 diabetes patients. TYK2PV status was determined using direct DNA sequencing and its associations with fasting insulin, C-peptide, and homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated in type 2 diabetes patients without sulfonylurea or insulin medication. Of the 172 patients assessed, 18 (10.5%) showed TYK2PV-positivity. Their body mass index (BMI) was significantly lower than in those without the variant (23.4 vs. 25.4 kg/m2, p = 0.025). Fasting insulin (3.9 vs. 6.2 μIU/mL, p = 0.007), C-peptide (1.37 vs. 1.76 ng/mL, p = 0.008), and HOMA-IR (1.39 vs. 2.05, p = 0.006) were lower in those with than in those without the variant. Multivariable analysis identified that TYK2PV was associated with fasting insulin ≤ 5 μIU/mL (odds ratio (OR) 3.63, p = 0.025) and C-peptide ≤ 1.0 ng/mL (OR 3.61, p = 0.028), and also lower insulin resistance (HOMA-IR ≤ 2.5; OR 8.60, p = 0.042). TYK2PV is associated with impaired insulin secretion and low insulin resistance in type 2 diabetes. Type 2 diabetes patients with TYK2PV should be carefully followed in order to receive the appropriate treatment including insulin injections.
登录
查看更多内容
影响因子：
6.7
作者：
Lazear HM;Lancaster A;Wilkins C;Suthar MS;Huang A;Vick SC;Clepper L;Thackray L;Brassil MM;Virgin HW;Nikolich-Zugich J;Moses AV;Gale M Jr;Früh K;Diamond MS
通讯作者：
Diamond MS
影响因子：
30.8
作者：
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium;Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium;South Asian Type 2 Diabetes (SAT2D) Consortium;Mexican American Type 2 Diabetes (MAT2D) Consortium;Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium;Mahajan A;Go MJ;Zhang W;Below JE;Gaulton KJ;Ferreira T;Horikoshi M;Johnson AD;Ng MC;Prokopenko I;Saleheen D;Wang X;Zeggini E;Abecasis GR;Adair LS;Almgren P;Atalay M;Aung T;Baldassarre D;Balkau B;Bao Y;Barnett AH;Barroso I;Basit A;Been LF;Beilby J;Bell GI;Benediktsson R;Bergman RN;Boehm BO;Boerwinkle E;Bonnycastle LL;Burtt N;Cai Q;Campbell H;Carey J;Cauchi S;Caulfield M;Chan JC;Chang LC;Chang TJ;Chang YC;Charpentier G;Chen CH;Chen H;Chen YT;Chia KS;Chidambaram M;Chines PS;Cho NH;Cho YM;Chuang LM;Collins FS;Cornelis MC;Couper DJ;Crenshaw AT;van Dam RM;Danesh J;Das D;de Faire U;Dedoussis G;Deloukas P;Dimas AS;Dina C;Doney AS;Donnelly PJ;Dorkhan M;van Duijn C;Dupuis J;Edkins S;Elliott P;Emilsson V;Erbel R;Eriksson JG;Escobedo J;Esko T;Eury E;Florez JC;Fontanillas P;Forouhi NG;Forsen T;Fox C;Fraser RM;Frayling TM;Froguel P;Frossard P;Gao Y;Gertow K;Gieger C;Gigante B;Grallert H;Grant GB;Grrop LC;Groves CJ;Grundberg E;Guiducci C;Hamsten A;Han BG;Hara K;Hassanali N;Hattersley AT;Hayward C;Hedman AK;Herder C;Hofman A;Holmen OL;Hovingh K;Hreidarsson AB;Hu C;Hu FB;Hui J;Humphries SE;Hunt SE;Hunter DJ;Hveem K;Hydrie ZI;Ikegami H;Illig T;Ingelsson E;Islam M;Isomaa B;Jackson AU;Jafar T;James A;Jia W;Jöckel KH;Jonsson A;Jowett JB;Kadowaki T;Kang HM;Kanoni S;Kao WH;Kathiresan S;Kato N;Katulanda P;Keinanen-Kiukaanniemi KM;Kelly AM;Khan H;Khaw KT;Khor CC;Kim HL;Kim S;Kim YJ;Kinnunen L;Klopp N;Kong A;Korpi-Hyövälti E;Kowlessur S;Kraft P;Kravic J;Kristensen MM;Krithika S;Kumar A;Kumate J;Kuusisto J;Kwak SH;Laakso M;Lagou V;Lakka TA;Langenberg C;Langford C;Lawrence R;Leander K;Lee JM;Lee NR;Li M;Li X;Li Y;Liang J;Liju S;Lim WY;Lind L;Lindgren CM;Lindholm E;Liu CT;Liu JJ;Lobbens S;Long J;Loos RJ;Lu W;Luan J;Lyssenko V;Ma RC;Maeda S;Mägi R;Männisto S;Matthews DR;Meigs JB;Melander O;Metspalu A;Meyer J;Mirza G;Mihailov E;Moebus S;Mohan V;Mohlke KL;Morris AD;Mühleisen TW;Müller-Nurasyid M;Musk B;Nakamura J;Nakashima E;Navarro P;Ng PK;Nica AC;Nilsson PM;Njølstad I;Nöthen MM;Ohnaka K;Ong TH;Owen KR;Palmer CN;Pankow JS;Park KS;Parkin M;Pechlivanis S;Pedersen NL;Peltonen L;Perry JR;Peters A;Pinidiyapathirage JM;Platou CG;Potter S;Price JF;Qi L;Radha V;Rallidis L;Rasheed A;Rathman W;Rauramaa R;Raychaudhuri S;Rayner NW;Rees SD;Rehnberg E;Ripatti S;Robertson N;Roden M;Rossin EJ;Rudan I;Rybin D;Saaristo TE;Salomaa V;Saltevo J;Samuel M;Sanghera DK;Saramies J;Scott J;Scott LJ;Scott RA;Segrè AV;Sehmi J;Sennblad B;Shah N;Shah S;Shera AS;Shu XO;Shuldiner AR;Sigurđsson G;Sijbrands E;Silveira A;Sim X;Sivapalaratnam S;Small KS;So WY;Stančáková A;Stefansson K;Steinbach G;Steinthorsdottir V;Stirrups K;Strawbridge RJ;Stringham HM;Sun Q;Suo C;Syvänen AC;Takayanagi R;Takeuchi F;Tay WT;Teslovich TM;Thorand B;Thorleifsson G;Thorsteinsdottir U;Tikkanen E;Trakalo J;Tremoli E;Trip MD;Tsai FJ;Tuomi T;Tuomilehto J;Uitterlinden AG;Valladares-Salgado A;Vedantam S;Veglia F;Voight BF;Wang C;Wareham NJ;Wennauer R;Wickremasinghe AR;Wilsgaard T;Wilson JF;Wiltshire S;Winckler W;Wong TY;Wood AR;Wu JY;Wu Y;Yamamoto K;Yamauchi T;Yang M;Yengo L;Yokota M;Young R;Zabaneh D;Zhang F;Zhang R;Zheng W;Zimmet PZ;Altshuler D;Bowden DW;Cho YS;Cox NJ;Cruz M;Hanis CL;Kooner J;Lee JY;Seielstad M;Teo YY;Boehnke M;Parra EJ;Chambers JC;Tai ES;McCarthy MI;Morris AP
通讯作者：
Morris AP
影响因子：
16.2
作者：
Davis, TME;Cull, CA;Holman, RR
通讯作者：
Holman, RR
影响因子：
158.5
作者：
Holman, Rury R.;Paul, Sanjoy K.;Neil, H. Andrew W.
通讯作者：
Neil, H. Andrew W.
影响因子：
4.5
作者：
Lontchi-Yimagou, Eric;Legoff, Jerome;Sobngwi, Eugene
通讯作者：
Sobngwi, Eugene