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dc.contributor.authorReinauer, C
dc.contributor.authorRosenbauer, J
dc.contributor.authorBächle, C
dc.contributor.authorHerder, C
dc.contributor.authorRoden, M
dc.contributor.authorEllard, S
dc.contributor.authorDe Franco, E
dc.contributor.authorKarges, B
dc.contributor.authorHoll, RW
dc.contributor.authorEnczmann, J
dc.contributor.authorMeissner, T
dc.date.accessioned2018-04-06T09:59:29Z
dc.date.issued2017-05-19
dc.description.abstractINTRODUCTION: Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA)DRandDQhaplotypes in a cohort with early-onset (age < 5 years), long term type 1 diabetes (T1D) and explored their influence on clinical and laboratory parameters. METHODS: Intermediate resolutionHLA-DRB1,DQA1andDQB1typing was performed in 233 samples from the German Paediatric Diabetes Biobank and compared with a local control cohort of 19,544 cases. Clinical follow-up data of 195 patients (diabetes duration 14.2 ± 2.9 years) and residual C-peptide levels were compared between three HLA risk groups using multiple linear regression analysis. RESULTS: Genetic variability was low, 44.6% (104/233) of early-onset T1D patients carried the highest-risk genotypeHLA-DRB1*03:01-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03:02(HLA-DRB1*04denoting04:01/02/04/05), and 231 of 233 individuals carried at least one of six risk haplotypes. Comparing clinical data between the highest (n= 83), moderate (n= 106) and low risk (n= 6) genotypes, we found no difference in age at diagnosis (mean age 2.8 ± 1.1 vs. 2.8 ± 1.2 vs. 3.2 ± 1.5 years), metabolic control, or frequency of associated autoimmune diseases between HLA risk groups (eachp> 0.05). Residual C-peptide was detectable in 23.5% and C-peptide levels in the highest-risk group were comparable to levels in moderate to high risk genotypes. CONCLUSION: In this study, we saw no evidence for a different clinical course of early-onset T1D based on the HLA genotype within the first ten years after manifestation.en_GB
dc.description.sponsorshipThis work was supported by the Ministry of Science and Research of the State of North Rhine-Westphalia (MIWF NRW) and the German Federal Ministry of Health (BMG). This study was supported in part by a grant by the Federal Ministry of Education and Research (BMBF) to the Competence Network Competence Network for Diabetes mellitus (support codes 01GI0802, 01GI1109A, 01GI1106) now integrated into the German Center for Diabetes Research (DZD). The DPV registry is additionally supported by the German Diabetes Association (DDG) and the European Foundation for the Study of Diabetes (EFSD), the Bürger-Brüsing Foundation, and EU IMI projects DIRECT and Innodia. Sian Ellard is a Wellcome Trust Senior Investigator (grant number WT098395/Z/12/Z).en_GB
dc.identifier.citationVol. 8 (5), article 146en_GB
dc.identifier.doi10.3390/genes8050146
dc.identifier.urihttp://hdl.handle.net/10871/32344
dc.language.isoenen_GB
dc.publisherMDPIen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/28534863en_GB
dc.rights© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en_GB
dc.subjectC-peptideen_GB
dc.subjectMHC IIen_GB
dc.subjectautoimmunityen_GB
dc.subjectdiabetes mellitusen_GB
dc.subjecthuman leukocyte antigenen_GB
dc.titleThe Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotypeen_GB
dc.typeArticleen_GB
dc.date.available2018-04-06T09:59:29Z
dc.identifier.issn2073-4425
exeter.place-of-publicationSwitzerlanden_GB
dc.descriptionThis is the final version of the article. Available from MDPI via the DOI in this record.en_GB
dc.identifier.journalGenesen_GB


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