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Role of HLA-DPrs3077 and HLA-DQrs3920 Polymorphisms as Risk Factors for Type 1 Diabetes Mellitus
- Source: Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders), Volume 23, Issue 6, May 2023, p. 850 - 856
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- 01 May 2023
Abstract
Background: Type 1 diabetes mellitus (T1DM) is a chronic disease caused by the destruction of insulin-producing pancreatic β-cells. During disease progression, inflammatory insulitis increases the presentation of islet antigens on human leukocyte antigen (HLA) molecules to T lymphocytes. This complex system plays a pivotal role in cellular immunity. Thus, genetic variability in HLA can affect the susceptibility to and clinical outcomes of DM. Aim: This case-control study aimed to assess the role of HLA-DP-rs3077 (A/G) and HLA-DQrs3920 (A/G) polymorphism in T1DM. Subjects and Methods: This study enrolled 400 individuals: 200 patients with T1DM and 200 ageand sex-matched healthy controls. Hemoglobin A1C and random, fasting, and postprandial blood sugar levels were determined for all subjects. Genotypic and allelic distributions of HLA-DPrs3077 (A/G) and HLA-DQrs3920 (A/G) SNPs were determined using real-time polymerase chain reaction (PCR). Results: Frequency of the HLA-DPrs3077A allele was high among the diabetic group (91.3%); however, the difference was non-significant [OR (95% C.I) = 1.422(0.89-2.252), P=0.098]. The frequency of the HLA-DQrs3920 GG genotype was higher in control than the diabetic group (52.5% vs.12%), whereas that of the AA genotype was higher in the person with diabetes than in the control group (34% vs.4%). Individuals carrying the HLA-DQrs3920A allele were 4.5 times more likely to have T1DM than those carrying the G allele [OR (95% C.I) = 4.510 (3.338- 6.094), P<0.001*]. The presence of HLA-DPrs3077A and HLA-DQ rs3920A in the same person increases T1DM risk by 3.6 times that of G allele [OR (95%C.I) = 3.608(2.173-5.991), P<0.001*]. Conclusion: HLA-DPrs3077 and HLA-DQrs3920 SNPs have a role in T1DM as the coexistence of HLA-DPrs3077A and HLA-DQrs3920A alleles increases the risk.