Abstract
Background
Interleukin-1 receptor antagonist (IL1RN) variable number tandem repeats (VNTRs) are not fully understood in Type 1 diabetes mellitus (T1DM). It may affect IL1RN level and modify the disease risk. We aimed to study IL1RN VNTR polymorphism in Egyptian children with T1DM to clarify its potential role as a risk factor for T1DM and its effect on plasma IL1RN level.
Methods
A case-controlled study including 200 children (120 T1DM and 80 controls) was carried on. All children were subjected to genotyping of IL1RN VNTR. Plasma IL1RN was estimated by ELISA.
Results
The A1A2 and LS genotypes and A2 allele were significantly higher among cases compared to controls with increased T1DM risk (OR = 5.35, 2.56 and 3.13, respectively). The S allele was significantly elevated in cases compared to controls with 2.09-fold increased risk of having T1DM. The median plasma IL1RN significantly decreased in cases compared to controls. Within cases, IL1RN was significantly decreased in LS versus LL genotype.
Conclusions
There is a strong relationship between IL1RN VNTR and T1DM in Egyptian children. A1A1 genotype, LL genotype, A1 allele, and L allele were protective. A1A2 and LS genotypes, short (S), and A2 alleles were risk factors. IL1RN was decreased in T1DM, especially in LS genotype.
Impact
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The relationship between IL1RN gene polymorphism and risk for T1DM among Egyptian children.
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Plasma IL1RN protein level in T1DM.
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Low IL1RN protein level in T1DM patients could be therapeutic targets for IL1RN medications in the future.
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Acknowledgements
Authors would like to thank all children and their parents who participated in this study. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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N.T.A., S.A.M., and E.M.E.-S.: contributed to the design and implementation of the research, aided in choosing the patients and helped shape the research, supervised the findings of this work, discussed the results, read and approved the final manuscript. I.A.R.: contributed to the design and implementation of the research, aided in choosing the patients, performed the laboratory work and helped shape the research, supervised the findings of this work, discussed the results, read and approved the final manuscript.
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The current study was approved by the Medical Research Ethical Committee of the Faculty of Medicine, Benha University. All subjects were informed about the procedures and the aim of the study, and informed written consent was obtained from the parents or caregivers of enrolled children. The committee’s reference number is not available.
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Abed, N.T., Ramadan, I.A., Mohammed, S.A. et al. Genetic polymorphism of interleukin-1 receptor antagonist in Type 1 diabetic children. Pediatr Res 91, 1536–1541 (2022). https://doi.org/10.1038/s41390-021-01569-5
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DOI: https://doi.org/10.1038/s41390-021-01569-5
