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Sequence analysis o...
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Pugliese, Alberto
(author)
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
- Article/chapterEnglish1999
Publisher, publication year, extent ...
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The Endocrine Society,1999
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-62807
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-62807URI
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https://doi.org/10.1210/jc.84.5.1722DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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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Added entries (persons, corporate bodies, meetings, titles ...)
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Kawasaki, Eiji
(author)
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Zeller, Markus
(author)
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Yu, Liping
(author)
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Babu, Sunanda
(author)
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Solimena, Michele
(author)
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Moraes, Carlos T.
(author)
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Pietropaolo, Massimo
(author)
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Friday, Robert P.
(author)
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Trucco, Massimo
(author)
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Ricordi, Camillo
(author)
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Allen, MarieUppsala universitet,Genomik(Swepub:uu)marialle
(author)
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Noble, Janelle A.
(author)
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Erlich, Henry A.
(author)
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Eisenbarth, George S.
(author)
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Uppsala universitetGenomik
(creator_code:org_t)
Related titles
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In:Journal of Clinical Endocrinology and Metabolism: The Endocrine Society84:5, s. 1722-17280021-972X1945-7197
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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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Moraes, Carlos T ...
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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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Uppsala University