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HLA Class II (DR, D...
HLA Class II (DR, DQ, DP) Genes Were Separately Associated With the Progression From Seroconversion to Onset of Type 1 Diabetes Among Participants in Two Diabetes Prevention Trials (DPT-1 and TN07)
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- Zhao, Lue Ping (author)
- Fred Hutchinson Cancer Research Center
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- Papadopoulos, George K (author)
- Technological Educational Institute of Epirus
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- Skyler, Jay S (author)
- University of Miami
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Pugliese, Alberto (author)
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- Parikh, Hemang M (author)
- University of South Florida
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- Kwok, William W (author)
- Benaroya Research Institute
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- Lybrand, Terry P (author)
- Vanderbilt University
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- Bondinas, George P (author)
- Ionian University
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- Moustakas, Antonis K (author)
- Ionian University
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- Wang, Ruihan (author)
- Fred Hutchinson Cancer Research Center
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- Pyo, Chul-Woo (author)
- Fred Hutchinson Cancer Research Center
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- Nelson, Wyatt C (author)
- Fred Hutchinson Cancer Research Center
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- Geraghty, Daniel E (author)
- Fred Hutchinson Cancer Research Center
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- Lernmark, Åke (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- English.
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In: Diabetes Care. - 1935-5548.
- Related links:
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http://dx.doi.org/10...
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Abstract
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- OBJECTIVE: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression.RESULTS: 1) The current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). 2) After adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). 3) DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). 4) Through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression.CONCLUSIONS: These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Zhao, Lue Ping
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Papadopoulos, Ge ...
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Skyler, Jay S
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Pugliese, Albert ...
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Parikh, Hemang M
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Kwok, William W
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show more...
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Lybrand, Terry P
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Bondinas, George ...
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Moustakas, Anton ...
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Wang, Ruihan
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Pyo, Chul-Woo
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Nelson, Wyatt C
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Geraghty, Daniel ...
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Lernmark, Åke
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetes Care
- By the university
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Lund University