PTPN22 C1858T polymorphism confers risk for familial type 1 diabetes in Moroccan children and adolescents

Abstract Background Type 1 diabetes (T1D) is a lifelong autoimmune condition characterised by the progressive immune-mediated destruction of insulin-secreting β-cells within the pancreatic islets, culminating in absolute insulin deficiency. Genetic susceptibility is a major determinant of disease development, involving both HLA and non-HLA immune regulatory genes. Among non-HLA candidates, the PTPN22 gene has been reproducibly linked to a broad spectrum of autoimmune diseases, including T1D. However, evidence from North African populations remains limited. The present study therefore examined the association between the PTPN22 C1858T (rs2476601) polymorphism and familial T1D risk in Moroccan children and adolescents. Methods A case-control study was conducted including 102 pediatric patients with T1D and 150 age- and sex-matched healthy controls. Genomic DNA was extracted from all participants, and the PTPN22 C1858T SNP was genotyped using a TaqMan ® real-time PCR assay. Allele and genotype frequencies were compared between groups using Fisher’s exact test, and logistic regression was used to assess the association with T1D risk. Results Marked disparities in genotype and allele distributions were detected between patients and controls. The CT genotype was present in 7.84% of patients but only 0.7% of controls (OR = 13.1, 95% CI: 1.61–106.46, p < 0.001), and the TT genotype was absent in the control group. The T allele frequency was higher in patients (6.9%) than in controls (0.3%) and was associated with an increased risk of T1D (OR = 22.03, 95% CI: 2.87–168.9, p < 0.001). Notably, all three patients carrying the TT genotype were diagnosed at age ≤ 5 years, indicating that this variant may be linked to earlier disease onset. Conclusions To our knowledge, this is the first study to establish that the PTPN22 C1858T variant confers T1D susceptibility in a Moroccan pediatric population. The results indicate that this genetic variant may contribute both to disease risk and to earlier onset of T1D. Further large-scale and functional studies are warranted to elucidate the biological mechanisms underlying this association and to explore its potential value in early diagnosis and prevention.