The Relationship between T1DM and the Polymorphisms of IL2RA (Rs2104286) and PTPN22 (Rs2476601) Genes among Children

Main Article Content

Ashjan Saad Metroid
Aalaa Abdulzahra Chmagh
Khwam Reissan Hussein
Mahmood Thamer Altemimi

Abstract

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune condition caused by T lymphocytes that results in the death of pancreatic cells. Protein tyrosine phosphate non-receptor type 22 (PTPN22) and interleukin 2 receptor alpha (IL2RA) polymorphisms have been discovered to have a connection to a number of autoimmune illnesses, including T1D.


Objective: The purpose of this study is to clarify the significance of the polymorphisms PTPN22 (rs2476601) and IL2RA (rs2104286) in the susceptibility to T1DM in young Iraqi children.


Methods: The study included 60 Iraqi children diagnosed with T1DM within the past three years and a control group of 30 healthy individuals without diabetes or autoimmune diseases. In order to conduct a molecular investigation. Five ml of venous blood from 90 participants (60 patients and 30 controls) was collected for nucleic acid extraction.


Results: The PTPN22 (rs2476601) and IL2RA (rs2104286) polymorphisms were genotyped using the amplification refractory mutation system (ARMS) technique and specific primers. According to the results, PTPN22 (rs2476601) has a wild-type homozygous C/C genotype and C allele frequency of 90%, a mutant C/T genotype frequency of 10%, and no T allele. Following were the genotype frequencies for IL2RA (rs2104286): AA, AG, and GG in T1DM patients were 79%, 16%, and 4%, respectively, compared to 83%, 13%, and 3% in controls.


Conclusion: The polymorphisms of PTPN22 rs2476601 and IL2RA rs2104286 did not significantly differ in their connection with type 1 diabetes. It does not appear to affect the susceptibility of Asian Iraqis to T1D.

Article Details

How to Cite
Metroid, A. S. ., Aalaa Abdulzahra Chmagh, Khwam Reissan Hussein, & Mahmood Thamer Altemimi. (2023). The Relationship between T1DM and the Polymorphisms of IL2RA (Rs2104286) and PTPN22 (Rs2476601) Genes among Children . International Journal of Medical Science and Clinical Research Studies, 3(9), 1927–1933. https://doi.org/10.47191/ijmscrs/v3-i9-22
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References

I. Akil, A. A. S. et al. Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era. J. Transl. Med. 19, 1–19 (2021).

II. Calabrese, C. M., Valentini, A. & Calabrese, G. Gut Microbiota and Type 1 Diabetes Mellitus: The Effect of Mediterranean Diet. Front. Nutr. 7, (2021).

III. Lu, X. & Zhao, C. Exercise and Type 1 Diabetes. Adv. Exp. Med. Biol. 1228, 107–121 (2020).

IV. Richardson, S. J. & Morgan, N. G. Enteroviral infections in the pathogenesis of type 1 diabetes: new insights for therapeutic intervention. Curr. Opin. Pharmacol. 43, 11–19 (2018).

V. Pasquel, F. J., Lansang, M. C., Dhatariya, K. & Umpierrez, G. E. Management of diabetes and hyperglycaemia in the hospital. Lancet Diabetes Endocrinol. 9, 174–188 (2021).

VI. Gerstein, H. C. & Rutty, C. J. Insulin Therapy: The Discovery That Shaped a Century. Can. J. Diabetes 45, 798–803 (2021).

VII. Mancuso, G., Genzano, C. B., Fierabracci, A. & Fousteri, G. Type 1 diabetes and inborn errors of immunity: Complete strangers or 2 sides of the same coin? J. Allergy Clin. Immunol. (2023).

VIII. Abdelrahman, H. M. et al. The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children. Hum. Immunol. 77, 682–686 (2016).

IX. Redondo, M. J., Steck, A. K. & Pugliese, A. Genetics of type 1 diabetes. Pediatr. Diabetes 19, 346–353 (2018).

X. Welter, M. et al. Polymorphism rs2476601 in the PTPN22 gene is associated with type 1 diabetes in children from the South Region of Brazil. Gene 650, 15–18 (2018).

XI. Tizaoui, K. et al. Genetic polymorphism of PTPN22 in autoimmune diseases: a comprehensive review. Medicina (B. Aires). 58, 1034 (2022).

XII. Pol, J. G., Caudana, P., Paillet, J., Piaggio, E. & Kroemer, G. Effects of interleukin-2 in immunostimulation and immunosuppression. J. Exp. Med. 217, 1–15 (2020).

XIII. Ahmadi, M., Hosseini, M., Aslani, S., Ayoubi-joshaghani, M. H. A. & Shirvani, B. Association between interleukin 2 receptor A gene polymorphisms (rs2104286 and rs12722489) with susceptibility to Multiple sclerosis in Iranian population. (2019).

XIV. Kouhpayeh, H. R. et al. R620W functional polymorphism of protein tyrosine phosphatase non-receptor type 22 is not associated with pulmonary tuberculosis in Zahedan, southeast Iran. Genet Mol Res 11, 1075–1081 (2012).

XV. Bottini, N. et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat. Genet. 36, 337–338 (2004).

XVI. Onengut-Gumuscu, S., Ewens, K. G., Spielman, R. S. & Concannon, P. A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes Immun. 5, 678–680 (2004).

XVII. Ptpn, P. & Diabetes, T. Brief Genetics Report. 906–908 (2005).

XVIII. Kahles, H. et al. Sex-specific association of PTPN22 1858T with type 1 diabetes but not with Hashimoto’s thyroiditis or Addison’s disease in the German population. Eur. J. Endocrinol. 153, 895–899 (2005).

XIX. Douroudis, K. et al. Protein tyrosine phosphatase non-receptor type 22 gene variants at position 1858 are associated with type 1 and type 2 diabetes in Estonian population. Tissue Antigens 72, 425–430 (2008).

XX. Zoledziewska, M. et al. Further evidence of a primary, causal association of the PTPN22 620W variant with type 1 diabetes. Diabetes 57, 229–234 (2008).

XXI. Korolija, M. et al. Association of PTPN22 C1858T and CTLA-4 A49G polymorphisms with type 1 diabetes in Croatians. Diabetes Res. Clin. Pract. 86, 54–57 (2009).

XXII. Sharma, C. et al. Association of variants in PTPN22, CTLA‐4, IL2‐RA, and INS genes with type 1 diabetes in Emiratis. Ann. Hum. Genet. 85, 48–57 (2021).

XXIII. Zhebrun, D. et al. Association of PTPN22 1858T/T genotype with type 1 diabetes, Graves’ disease but not with rheumatoid arthritis in Russian population. Aging (Albany. NY). 3, 368–373 (2011).

XXIV. Kawasaki, E. et al. Systematic Search for Single Nucleotide Polymorphisms in a Lymphoid Tyrosine Phosphatase Gene ( PTPN22 ): Association Between a Promoter Polymorphism and Type 1 Diabetes in Asian Populations. 593, 586–593 (2006).

XXV. Pei, Z. et al. Research : Genetics A novel single nucleotide polymorphism in the protein tyrosine phosphatase N22 gene ( PTPN22 ) is associated with Type 1 diabetes in a Chinese population. 22, 219–226 (2013).

XXVI. Editor, D. No evidence for association of PTPN22 R620W functional variant C1858T with type 1 diabetes in Asian Indians. 12, 1061–1062 (2008).

XXVII. Abbasi, F. et al. PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus. Immunol. Invest. 46, 409–418 (2017).

XXVIII. Ferjani, Z. et al. Association between the IL2RA polymorphism and type 1 diabetes risk: Family based association study. Meta Gene 10, 118–122 (2016).

XXIX. Alcina, A. et al. IL2RA/CD25 gene polymorphisms: Uneven association with multiple sclerosis (MS) and type 1 diabetes (T1D). PLoS One 4, 1–5 (2009).

XXX. Fichna, M., Zurawek, M., Fichna, P., Januszkiewicz, D. & Nowak, J. Polymorphic variants of the IL2RA gene and susceptibility to type 1 diabetes in the Polish population. Tissue Antigens 79, 198–203 (2012).

XXXI. Abou El Ella, S. S., Tawfik, M. A., Mohammed, Z. S. & Barseem, N. F. PTPN22 gene and IL2RA rs11594656, rs2104286 gene variants: additional insights of polygenic single-nucleotide polymorphisms’ pattern among Egyptian children with type 1 diabetes. Egypt. Pediatr. Assoc. Gaz. 69, (2021).

XXXII. Tang, W. et al. Association of common polymorphisms in the IL2RA gene with type 1 diabetes: Evidence of 32,646 individuals from 10 independent studies. J. Cell. Mol. Med. 19, 2481–2488 (2015).

XXXIII. Butter, F. et al. Proteome-Wide Analysis of Disease-Associated SNPs That Show Allele-Specific Transcription Factor Binding. PLoS Genet. 8, (2012).

XXXIV. Lowe, C. E. et al. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat. Genet. 39, 1074–1082 (2007).