eISSN: 2083-8441
ISSN: 2081-237X
Pediatric Endocrinology Diabetes and Metabolism
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2/2020
vol. 26
 
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abstract:
Original paper

HLA-A gene variation modulates residual function of the pancreatic β-cells in children with type 1 diabetes

Anna Hogendorf
1
,
Michał Abel
2
,
Krystyna Wyka
3
,
Jerzy Bodalski
2
,
Wojciech Młynarski
3

1.
Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Poland
2.
Department of Pediatrics, Medical University of Lodz, Poland
3.
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Pediatr Endocrinol Diabetes Metab 2020; 26 (2): 73–78
Online publish date: 2020/05/27
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Aim of the study
The study aimed to analyze an association between the HLA-A gene variation and a risk of type 1 diabetes development and to evaluate the association of HLA class I and class II alleles with β-cell destruction.

Material and methods
A group of 108 children with type 1 diabetes were genotyped in HLA-A, -DRB1, and -DQB1 genes using hybridization with oligonu-cleotides probes. Plasma C-peptide concentration was assessed by radioimmunoassay method.

Results
No differences in allele HLA-A distribution between type 1 diabetes patients and healthy individuals were found. Among “low C-peptide”(< 0.28 pmol/ml) individuals, the frequency of HLA-A*02 allele was 41.3%, whereas only one HLA-A*26 allele was detected in this group (0.7%). Conversely, among “high C-peptide”( 0.28 pmol/ml) probands the prevalence of A*02 allele was 19.7% (Pc = 0.008, OR = 1.4, 95% CI: 1.2–1.7) and A*26 10.5 % (Pc < 0.007, OR = 0.15, 95% CI: 0.02–0.9). Genotype analysis showed that A*02/*02 and A*02/X children were more likely to have “low” C-peptide at the onset compared to those with non-A*02/non-A*02 genotype (p = 0.008, OR = 1.6, 95% CI: 1.3–2.0 and p = 0.015, OR = 1.4, 95% CI: 1.1–1.9, respectively). A02 phenotype individuals had lower median C-peptide (0.17 pmol/ml) than non-A02 patients (0.26 pmol/ml, p = 0.008). Median C-peptide was higher in the A26-positive group comparing to A26-negative (0.40 and 0.20, respectively, p = 0.04). No association between HLA class II and C-peptide levels was observed.

Conclusions
HLA-A alleles are not associated with disease development nevertheless strongly influence a residual pancreatic β-cell function. The results suggest a different role of HLA class I and class II in type 1 diabetes pathogenesis.

keywords:

type 1 diabetes, HLA-A HLA-DR, HLA-DQ, C-peptide, genetic predisposition, disease progression, β-cell destruction

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