类逆转录病毒样长末端重复序列DQ-LTR13与1型糖尿病和自身免疫性艾迪生病的遗传易感性

Retrovirus-like long-terminal repeat DQ-LTR13 and genetic susceptibility to type 1 diabetes and autoimmune Addison's disease.

作者信息

Gambelunghe Giovanni, Kockum Ingrid, Bini Vittorio, De Giorgi Giovanni, Celi Federica, Betterle Corrado, Giordano Roberta, Libè Rossella, Falorni Alberto

机构信息

Department of Internal Medicine, University of Perugia, Via E. Dal Pozzo, I-06126 Perugia, Italy.

出版信息

Diabetes. 2005 Mar;54(3):900-5. doi: 10.2337/diabetes.54.3.900.

DOI:10.2337/diabetes.54.3.900

PMID:15734871

Abstract

Controversial data are available on the association between the retrovirus-like long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic patients, 166 autoimmune Addison's disease (AAD) patients, 1,054 healthy subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more frequent among patients than healthy subjects (P(c) < 0.0006), and a preferential transmission of DQB10302-LTR13(+) from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB10302 but not DQB10201. The presence of DQ-LTR13 increased the odds ratio of DQB10302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB10403 was absent in all of the 169 DRB104-positive patients but present in 27% (34 of 127) DRB104-positive healthy subjects (P(c) < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB10403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB104 allele (P(c) = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB10302 and DRB10403. Conversely, DQB10201, DQB10302, DRB10401, and DRB10403 were all significantly associated with disease risk also after correction for DQ-LTR13. We provide conclusive evidence that the genetic association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD with DQB10302 and DRB1*0403.

摘要

关于逆转录病毒样长末端重复序列（LTR）DQ-LTR13与1型糖尿病及其他自身免疫性疾病遗传易感性之间的关联，存在有争议的数据。我们分析了315例1型糖尿病患者、166例自身免疫性艾迪生病（AAD）患者、1054名健康受试者以及144个1型糖尿病患者后代家庭的DNA样本。DQ-LTR13在患者中的出现频率高于健康受试者（P(c) < 0.0006），并且观察到DQB10302-LTR13(+)从父母向1型糖尿病后代的优先传递。DQ-LTR13与DQB10302处于连锁不平衡（LD）状态，但与DQB10201不处于LD状态。DQ-LTR13的存在使1型糖尿病和AAD中DQB10302的优势比增加了2.9至3.2倍。在所有169例DRB104阳性患者中均未检测到DRB10403，但在27%（127例中的34例）DRB104阳性健康受试者中存在（P(c) < 0.001）。在34例DRB10403阳性健康受试者中有1例（3%）检测到DQ-LTR13，在携带另一个DRB104等位基因的93例个体中有36例（39%）检测到DQ-LTR13（P(c) = 0.002）。多因素逻辑回归分析显示，在校正DQB10302和DRB10403后，DQ-LTR13与1型糖尿病和AAD无独立关联。相反，在校正DQ-LTR13后，DQB10201、DQB10302、DRB10401和DRB10403也均与疾病风险显著相关。我们提供了确凿证据，表明DQ-LTR13与1型糖尿病和AAD的遗传关联主要是由于与DQB10302和DRB1*0403的连锁不平衡。