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

ABSTRACT

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 ß-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 ß-cell function. The results suggest a different role of HLA class I and class II in type 1 diabetes pathogenesis.