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Retrovirus-like lon...
Retrovirus-like long-terminal repeat DQ-LTR13 and genetic susceptibility to type 1 diabetes and autoimmune Addison's disease
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Gambelunghe, G (author)
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- Kockum, I (author)
- Karolinska Institutet
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Bini, V (author)
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De Giorgi, G (author)
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Celi, F (author)
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Betterle, C (author)
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Giordano, R (author)
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Libe, R (author)
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Falorni, A (author)
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(creator_code:org_t)
- American Diabetes Association, 2005
- 2005
- English.
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:3, s. 900-905
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https://doi.org/10.2...
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Abstract
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- 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 (Pc < 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 (Pc < 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 (Pc = 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.
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