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

Diabetes, ISSN: 0012-1797, Vol: 54, Issue: 3, Page: 900-905
2005
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Article Description

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 < 0.0006), and a preferential transmission of DQB1*0302-LTR13 from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with BQB1*0302 but not DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169 DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy subjects (P < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele (P = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB1*0302 and DRB1*0403. Conversely, DQB1*0201, DQB1*0302, DRB1*0401, and DRB1*0403 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 DQB1*0302 and DRB1*0403. © 2005 by the American Diabetes Association.

Bibliographic Details

Gambelunghe, Giovanni; Kockum, Ingrid; Bini, Vittorio; De Giorgi, Giovanni; Celi, Federica; Betterle, Corrado; Giordano, Roberta; Libè, Rossella; Falorni, Alberto; Umbria Type 1 Diabetes Registry; Italian Addison Network

American Diabetes Association

Medicine

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