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Sequence analysis o...
Sequence analysis of the diabetes-protective human leukocyte antigen-DQB1*0602 allele in unaffected, islet cell antibody-positive first degree relatives and in rare patients with type 1 diabetes
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Pugliese, Alberto (författare)
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Kawasaki, Eiji (författare)
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Zeller, Markus (författare)
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Yu, Liping (författare)
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Babu, Sunanda (författare)
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Solimena, Michele (författare)
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Moraes, Carlos T. (författare)
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Pietropaolo, Massimo (författare)
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Friday, Robert P. (författare)
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Trucco, Massimo (författare)
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Ricordi, Camillo (författare)
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- Allen, Marie (författare)
- Uppsala universitet,Genomik
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Noble, Janelle A. (författare)
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Erlich, Henry A. (författare)
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Eisenbarth, George S. (författare)
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(creator_code:org_t)
- The Endocrine Society, 1999
- 1999
- Engelska.
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 84:5, s. 1722-1728
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The human leukocyte antigen (HLA)-DQA1*0102/DQB1*0602/DRB1*1501 (DR2) haplotype confers strong protection from type 1 diabetes. Growing evidence suggests that such protection may be mostly encoded by the DQB1*0602 allele, and we reported that even first degree relatives with islet cell antibodies (ICA) have an extremely low diabetes risk if they carry DQB1*0602. Recently, novel variants of the DQB1*0602 and *0603 alleles were reported in four patients with type 1 diabetes originally typed as DQB1*0602 with conventional techniques. One inference from this observation is that DQB1*0602 may confer absolute protection and may never occur in type 1 diabetes. By this hypothesis, all patients typed as DQB1*0602 positive with conventional techniques should carry one of the above diabetes-permissive variants instead of the protective DQB1*0602. Such variants could also occur in ICA/DQB1*0602-positive relatives, with the implication that their diabetes risk could be significantly higher than previously estimated. We therefore sequenced the DQB1*0602 and DQA1*0102 alleles in all ICA/DQB1*0602-positive relatives (n = 8) previously described and in six rare patients with type 1 diabetes and DQB1*0602. We found that all relatives and patients carry the known DQB1*0602 and DQA1*0102 sequences, and none of them has the mtDNA A3243G mutation associated with late-onset diabetes in ICA-positive individuals. These findings suggest that diabetes-permissive DQB1*0602/3 variants may be very rare. Thus, although the protective effect associated with DQB1*0602 is extremely powerful, it is not absolute. Nonetheless, the development of diabetes in individuals with DQB1*0602 remains extremely unlikely, even in the presence of ICA, as confirmed by our further evaluation of ICA/DQB1*0602-positive relatives, none of whom has yet developed diabetes.
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- MEDICIN
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Pugliese, Albert ...
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Kawasaki, Eiji
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Zeller, Markus
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Yu, Liping
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Babu, Sunanda
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Solimena, Michel ...
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visa fler...
-
Moraes, Carlos T ...
-
Pietropaolo, Mas ...
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Friday, Robert P ...
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Trucco, Massimo
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Ricordi, Camillo
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Allen, Marie
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Noble, Janelle A ...
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Erlich, Henry A.
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Eisenbarth, Geor ...
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visa färre...
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Uppsala universitet