dc.contributor.author | Reinauer, C | |
dc.contributor.author | Rosenbauer, J | |
dc.contributor.author | Bächle, C | |
dc.contributor.author | Herder, C | |
dc.contributor.author | Roden, M | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | De Franco, E | |
dc.contributor.author | Karges, B | |
dc.contributor.author | Holl, RW | |
dc.contributor.author | Enczmann, J | |
dc.contributor.author | Meissner, T | |
dc.date.accessioned | 2018-04-06T09:59:29Z | |
dc.date.issued | 2017-05-19 | |
dc.description.abstract | INTRODUCTION: 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.sponsorship | This 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.citation | Vol. 8 (5), article 146 | en_GB |
dc.identifier.doi | 10.3390/genes8050146 | |
dc.identifier.uri | http://hdl.handle.net/10871/32344 | |
dc.language.iso | en | en_GB |
dc.publisher | MDPI | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/28534863 | en_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.subject | C-peptide | en_GB |
dc.subject | MHC II | en_GB |
dc.subject | autoimmunity | en_GB |
dc.subject | diabetes mellitus | en_GB |
dc.subject | human leukocyte antigen | en_GB |
dc.title | The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-04-06T09:59:29Z | |
dc.identifier.issn | 2073-4425 | |
exeter.place-of-publication | Switzerland | en_GB |
dc.description | This is the final version of the article. Available from MDPI via the DOI in this record. | en_GB |
dc.identifier.journal | Genes | en_GB |