Next Article in Journal
CpG and Non-CpG Methylation in Epigenetic Gene Regulation and Brain Function
Next Article in Special Issue
Effects of Type 1 Diabetes Risk Alleles on Immune Cell Gene Expression
Previous Article in Journal
Epigenetic Regulation of Telomere Maintenance for Therapeutic Interventions in Gliomas
Previous Article in Special Issue
Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Genes 2017, 8(5), 146; doi:10.3390/genes8050146

The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype

1
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
2
Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
3
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
4
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
5
Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
6
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter EX2 5DW, UK
7
Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
8
Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, 89069 Ulm, Germany
9
Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Roel Ophoff
Received: 30 January 2017 / Revised: 3 May 2017 / Accepted: 16 May 2017 / Published: 19 May 2017
(This article belongs to the Special Issue Genetics and Functional Genomics of Diabetes Mellitus)
View Full-Text   |   Download PDF [1160 KB, uploaded 19 May 2017]   |  

Abstract

Introduction: Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA) DR and DQ haplotypes 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 resolution HLA-DRB1, DQA1 and DQB1 typing 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 genotype HLA-DRB1*03:01-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03:02 (HLA-DRB1*04 denoting 04:01/02/04/05), 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 (each p > 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. View Full-Text
Keywords: MHC II; C-peptide; autoimmunity; human leukocyte antigen; diabetes mellitus MHC II; C-peptide; autoimmunity; human leukocyte antigen; diabetes mellitus
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Reinauer, C.; Rosenbauer, J.; Bächle, C.; Herder, C.; Roden, M.; Ellard, S.; De Franco, E.; Karges, B.; Holl, R.W.; Enczmann, J.; Meissner, T. The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype. Genes 2017, 8, 146.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top