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

INTRODUCTION

Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA) and 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 , and 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 ( denoting ), and 231 of 233 individuals carried at least one of six risk haplotypes. Comparing clinical data between the highest ( = 83), moderate ( = 106) and low risk ( = 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 > 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.