The Role of Two Protein Tyrosine Phosphatase, Non-Receptor Type 22(PTPN22) Gene Variants (rs2476601 and rs1310182) in the Development of Type 1 Diabetes

Abstract

Background: Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the destruction of pancreatic beta cells, which results in persistent hyperglycemia and requires lifelong insulin therapy. T1D results from complex genetic, epigenetic, and environmental interactions. Genetic factors account for up to 80% of hereditary T1D risk, while environmental and epigenetic influences also play important roles in disease development. Among the genetic factors identified, the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene has been implicated in T1D susceptibility. PTPN22 encodes the lymphoid specific phosphatase (LYP), which is a key negative regulator of T cell receptor signaling, thereby influencing immune tolerance and autoimmunity. Notably, two single nucleotide polymorphisms (SNPs) within PTPN22—rs2476601 and rs1310182—have been associated with variable risk for T1D, with their prevalence and impact differing across populations and geographic regions. Objective: The objective of this study is to examine the molecular genetic basis of T1D in a Palestinian cohort by screening for the rs2476601 and rs1310182 polymorphisms in the PTPN22 gene, aiming to clarify their potential association with T1D risk in this population. Methods: The study recruited a total of 205 individuals, comprising 100 confirmed T1D cases and 105 healthy controls, from the cities of Ramallah and Jenin. Genomic DNA was extracted from all participants and Sanger sequencing was utilized to identify the presence of the specified PTPN22 variants. Genotypic and allelic frequencies were compared between cases and controls to assess association with T1D. Results: Analysis of the genotypic and allelic distributions for both rs2476601 and rs1310182 polymorphisms revealed no statistically significant association with T1D in the studied cohort. These findings suggest that, within the Palestinian population, these specified PTPN22 variants do not confer an increased susceptibility to T1D. Conclusion: This study contributes to the growing body of evidence regarding the geographic variability of PTPN22 polymorphisms and their role in T1D. The lack of association observed emphasizes the need for larger sample size and the evaluation of additional genetic markers to comprehensively understand the genetic basis of T1D