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Journal of Diabetes & Metabolic Disorders

18-04-2024 | Type 1 Diabetes | Research article

Association of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants and type 1 diabetes mellitus

Authors: Noha M. Abd El-Fadeal, Manar A. Saad, Eman T. Mehanna, Hoda Atwa, Dina M. Abo-elmatty, Nora Hosny

Published in: Journal of Diabetes & Metabolic Disorders

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Abstract

Background

Type I diabetes mellitus (T1DM) is a significant health challenge, especially for children, owing to its chronic autoimmune nature. Although the exact etiology of T1DM remains elusive, the interplay of genetic predisposition, immune responses, and environmental factors are postulated. Genetic factors control immune reactivity against β-cells. Given the pivotal roles of CIITA and CLEC2D genes in modulating a variety of immune pathologies, we hypothesized that genetic variations in CIITA and CLEC2D genes may impact T1DM disease predisposition. This study was designed to explore the association between gene polymorphisms in CIITA (rs8048002) and CLEC2D (rs2114870) and type 1 diabetes (T1DM), with a focus on analyzing the functional consequence of those gene variants.

Methods

The study enlisted 178 healthy controls and 148 individuals with type 1 diabetes (T1DM) from Suez Canal University Hospital. Genotyping for CIITA and CLEC2D was done using allelic-discrimination polymerase chain reaction (PCR). Levels of glycated hemoglobin (HbA1c) and lipid profiles were determined through automated analyzer, while fasting blood glucose and insulin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RegulomeDB was used to examine the regulatory functions of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants.

Results

Analysis of the genotype distribution of the CIITA rs8048002 polymorphism revealed a significantly higher prevalence of the rare C allele in T1DM patients compared to the control group (OR = 1.77; P = 0.001). Both the CIITA rs8048002 heterozygote TC genotype (OR = 1.93; P = 0.005) and the rare homozygote CC genotype (OR = 3.62; P = 0.006) were significantly more frequent in children with T1DM when compared to the control group. Conversely, the rare A allele of CLEC2D rs2114870 was found to be significantly less frequent in T1DM children relative to the control group (OR = 0.58; P = 0.002). The heterozygote GA genotype (OR = 0.61; P = 0.033) and the rare homozygote AA genotype (OR = 0.25; P = 0.004) were also significantly less frequent in T1DM patients compared to the control group. Both CIITA (rs8048002) and CLEC2D (rs2114870) gene variants were predicted to have regulatory functions, indicated by a RegulomeDB score of (1f) for each.

Conclusion

The rare C allele of CIITA rs8048002 genetic variant was associated with an increased risk of developing T1DM, while the less common A allele of CLEC2D rs2114870 was associated with a reduced risk of T1DM.
Appendix
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Metadata
Title
Association of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants and type 1 diabetes mellitus
Authors
Noha M. Abd El-Fadeal
Manar A. Saad
Eman T. Mehanna
Hoda Atwa
Dina M. Abo-elmatty
Nora Hosny
Publication date
18-04-2024
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-024-01402-w
Obesity Clinical Trial Summary

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