Retrovirus-Like Long-Terminal Repeat DQ-LTR13 and Genetic Susceptibility to Type 1 Diabetes and Autoimmune Addison’s Disease

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 DQB1*0302-LTR13 ؉ from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*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 c < 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 c ‫؍‬ 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. Diabetes 54:900 -905, 2005

Autoimmunity to Steroid-Producing Cells

“…The DRB1*0401 subtype was strongly and positively associated with T1DM, but not with AAD (Yu et al, 1999;Myhre et al, 2002). However, an Italian study from our group (Gambelunghe et al, 2005) did not confirm this hypothesis. In that study (Gambelunghe et al, 2005), it was observed that no statistically different distribution of DRB1*0401 and DRB1*0404 was detectable among T1DM patients and AAD patients.…”

“…However, an Italian study from our group (Gambelunghe et al, 2005) did not confirm this hypothesis. In that study (Gambelunghe et al, 2005), it was observed that no statistically different distribution of DRB1*0401 and DRB1*0404 was detectable among T1DM patients and AAD patients. On the other hand, it was observed that the DRB1*0403 subtype, which was already known to confer strong protection for T1DM, was absent among 56 DRB1*04-positive AAD patients, but present in 27 % DRB1*04-positive healthy control subjects, thus conferring protection also for the development of AAD.…”

Recent advances in adrenal autoimmunity

“…The DRB1*0401 subtype was strongly and positively associated with T1DM, but not with AAD [107,108]. However, an Italian study by our group did not confirm this hypothesis [109]. In that study, it was observed that not statistically different distribution of DRB1*0401 and DRB1*0404 was detectable among T1DM patients and AAD patients.…”

Cooccurrences of Putative Endogenous Retrovirus-Associated Diseases

“…There is some evidence for the association of HERV-K18 polymorphisms with T1D [57, 58]. Moreover, there seems to be a link between the retrovirus-like long-terminal repeat DQ-LTR13 and the genetic susceptibility to T1D [59]. …”