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Published on: May 6, 2013
Associations between HLA class II alleles and type 1 diabetes mellitus in the Slovak population
1Department of Immunology, Comenius University School of Medicine, Czech Republic. milan.buc@fmed.uniba.sk
Insights
This study identified specific human leukocyte antigen (HLA) alleles, DQB1*0302 and DQA1*0301, as significantly associated with type 1A diabetes mellitus (DM-1A) in the Slovak population. These findings highlight key genetic markers for DM-1A risk in this demographic.
Area of Science:
- Immunogenetics
- Human Genetics
- Endocrinology
Background:
- Human leukocyte antigen (HLA) complex associations with type 1A diabetes mellitus (DM-1A) are established in Caucasian populations.
- No prior studies have investigated these associations within the Slovak population.
Purpose of the Study:
- To investigate the association between specific HLA-DQB1, HLA-DQA1, and HLA-DRB1 alleles and DM-1A in the Slovak population.
- To identify potential genetic markers for DM-1A risk in this specific ethnic group.
Main Methods:
- HLA typing was performed using the PCR-SSP method on 460 DM-1A patients and control groups.
- Specific alleles analyzed included HLA-DQB1 (460 patients), HLA-DQA1 (97 patients), and HLA-DRB1 (146 patients).
- Statistical analysis employed the Fisher exact test to compare allele frequencies between patients and healthy subjects.
Main Results:
- HLA-DQB1*0302 and DQB1*0201 were found at higher frequencies in DM-1A patients compared to healthy subjects.
- Conversely, DQB1*0301, DQB1*0602, and DQB1*0603 showed decreased frequencies in DM-1A patients.
- Specific HLA-DQA1 and HLA-DRB1 alleles were also identified with altered frequencies, with some forming characteristic haplotypes associated with DM-1A.
Conclusions:
- Specific HLA-DQB1, HLA-DQA1, and HLA-DRB1 alleles are significantly associated with DM-1A in the Slovak population.
- The identified alleles and haplotypes, particularly DQB1*0302/DQA1*0301 and DQB1*0201/DQA1*0501, serve as important genetic markers for DM-1A.
- This study provides crucial insights into the genetic predisposition of DM-1A in Slovaks, filling a gap in previous research.
Objectives:
Several associations between HLA complex and diabetes mellitus type IA were found in various groups of patients of Caucasoid population. This study was therefore prompted to be conducted in Slovak population, since any such has not yet been performed in Slovak population.
Methods:
Patients suffering from DM-1A originated from all regions of Slovakia. Their age ranged from 1 to 42 years; but the criterion for including the subject to the study was the definition of diagnosis in older patients before their age of 15 (Table 1). The diagnosis was set up according to internationally accepted criteria. A total of 460 patients was typed for HLA-DQB1 alleles, among them 97 also for HLA-DQA1 and 146 for HLA-DRB1 alleles. HLA-typing was performed by a PCR-SSP method. Control group consisted of 196 (DQA), 143 (DQB1) and 130 (DRB1) unrelated blood donors aged 19-55 years old irrespective of their age or sex. The data obtained were expressed in a 2 x 2 contingency table and statistical significance was calculated by the Fisher exact test.
Results:
Among 11 HLA-DQB1 alleles tested DOB1*0302 was the most frequent in DM-1A patients (30.33% vs. 5.59% in healthy subjects (HS), followed by DQB1*0201 (22.93% vs. 12.94%, respectively). In contrast, the frequency rate of DQB1*0301 (10.66% vs. 24.48%), DOB1*0602 (2.17% vs. 10.14%) and DQB1*0603 (2.5% vs. 8.39 %) were decreased in DM-1A patients. Out of 14 DQA1 alleles the highest occurrence rate showed DQA1*0301 (30.93% vs. 17.09) and DQA1*0501 (34.02% vs. 25.76%), while DQA1*0102 (8.76% vs. 16.58%) and DQA1*0201 (6.18 % vs. 13.51%7), respectively, were found to be the least frequent. Among 13 HLA-DRB1 alleles tested, the most common occurrence rates showed DRB1*03 (26.37% vs. 9.62%) and DRB1*04 (7.19% vs. 14.23%), while the least frequent alleles were DRB 1*15 (2.74% vs. 12.31%), DRB1*07 (7.19% vs. 14.23%), and DRB1*11 (2.74% vs. 20.38%). The alleles DQB1*0302 and DQA1*0301, respectively, were present in the same individual in all DRB1*04 positive patients, suggesting that they belong to the haplotype. Similar situation was observed with the alleles DQB1*0201, DQA1*0501, and DRB*0301, respectively, forming the second HLA haplotype so characteristic for DM1A.
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