DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life.
DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life.
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DOI：
10.1007/s00125-021-05513-4
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发表时间：
2021-10
期刊：
影响因子：
8.2
通讯作者：
Oram RA
中科院分区：
文献类型：
--
作者：
Thomas NJ;Dennis JM;Sharp SA;Kaur A;Misra S;Walkey HC;Johnston DG;Oliver NS;Hagopian WA;Weedon MN;Patel KA;Oram RA
在发生1型糖尿病的欧洲白色儿童中，其他常见的HLA单倍型DR 15-DQ 6是罕见的，并且具有高度保护性。现在已知成人发病的1型糖尿病比儿童发病的病例更多，但尚不清楚DR 15-DQ 6是否对老年人发病的1型糖尿病具有保护作用。我们试图量化DR 15-DQ 6对1型糖尿病发病年龄增加的保护作用。在两个独立的队列中，我们评估了与对照人群相比，在前50年中出现DR 15-DQ 6的1型糖尿病病例的比例。在糖尿病诊断后研究支持系统-2（ADDRESS-2）队列（n = 1458）中，临床医生诊断的1型糖尿病通过一种或多种胰岛特异性自身抗体阳性得到证实。在英国生物样本库（n = 2502）中，我们使用Poisson回归估计了每个HLA组相对于基线HLA风险的1型糖尿病发病率。分析仅限于白色欧洲人，并根据1型糖尿病发病时的年龄分为三组：0-18岁，19-30岁和31-50岁。DR 15-DQ 6对1型糖尿病具有保护作用，直至50岁（每个年龄组的OR < 1，所有p < 0.001）。在ADDRESS-2中观察到1型糖尿病相对于中性HLA基因型的以下OR：5-18岁OR 0.16（95% CI 0.08，0.31）; 19-30岁OR 0.10（0.04，0.23）; 31-50岁OR 0.37（0.21，0.68）。DR 15-DQ 6在英国生物库中的所有年龄段都保持高度保护性。在没有DR 15-DQ 6的情况下，主要1型糖尿病高危单倍型（DR 3-DQ 2或DR 4-DQ 8）的存在与1型糖尿病风险增加相关。HLA DR 15-DQ 6在生命的前50年内对1型糖尿病具有明显的保护作用。在线版本包含同行评审但未经编辑的补充材料，可通过10.1007/s 00125 -021-05513-4获得。
Among white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased. In two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-specific autoantibodies. In UK Biobank (n = 2502), we estimated type 1 diabetes incidence rates relative to baseline HLA risk for each HLA group using Poisson regression. Analyses were restricted to white Europeans and were performed in three groups according to age at type 1 diabetes onset: 0–18 years, 19–30 years and 31–50 years. DR15-DQ6 was protective against type 1 diabetes through to age 50 years (OR < 1 for each age group, all p < 0.001). The following ORs for type 1 diabetes, relative to a neutral HLA genotype, were observed in ADDRESS-2: age 5–18 years OR 0.16 (95% CI 0.08, 0.31); age 19–30 years OR 0.10 (0.04, 0.23); and age 31–50 years OR 0.37 (0.21, 0.68). DR15-DQ6 also remained highly protective at all ages in UK Biobank. Without DR15-DQ6, the presence of major type 1 diabetes high-risk haplotype (either DR3-DQ2 or DR4-DQ8) was associated with increased risk of type 1 diabetes. HLA DR15-DQ6 confers dominant protection from type 1 diabetes across the first five decades of life. The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05513-4.
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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：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1016/s2213-8587(17)30362-5
发表时间：
2018-03
期刊：
The lancet. Diabetes & endocrinology
影响因子：
--
作者：
Thomas NJ;Jones SE;Weedon MN;Shields BM;Oram RA;Hattersley AT
通讯作者：
Hattersley AT
影响因子：
2.7
作者：
DOHERTY, DG;VAUGHAN, RW;MOWAT, AP
通讯作者：
MOWAT, AP
影响因子：
3.5
作者：
Casu, A.;Kanapka, L. G.;Peters, A. L.
通讯作者：
Peters, A. L.