PTPN22 gene rs2476601 SNP is associated with type 1 diabetes and not anti-Gad autoantibodies in Egyptian children

Abstract

PTPN22 gene encodes lymphoid protein tyrosine phosphates (Lyp), which is a critical negative regulator of TCR signal transduction. A variant of PTPN22 (1858T) has been reportedly associated with the development and progress of T1DM. Since auto-reactive cytotoxic lymphocytes appear to be the main effector cells in T1DM, this might explain the reason of the aforementioned association. This study was conducted on 150 subjects; 100 T1DM patients and 50 controls; all were subjected to DNA analysis of PTPN22 C1858T polymorphism using PCR-RFLP technique, along with HbA1c%, Glutamic acid decarboxylase (GAD65) autoantibodies determinations. This study showed that 83 patients (83%) were homozygous for PTPN22 (CC), 15 patients (15%) were heterozygous for (CT) and 2 patients (2%) were homozygous for (TT). Statistical comparisons for the distribution of genotypes and allele frequency for the PTPN22 C1858T polymorphism between T1DM patients and controls showed that 17% of T1DM patients were TT/CT compared to 0% of controls (P = 0.002) and odds ratio [1.602 (1.404 to 1.828)]. Also, 181 alleles of T1DM patients were C (90.5%) compared to 100 alleles (100%) of controls with P value = 0.001. No significant associations between PTPN22 genotypes and other factors such as age, gender, age at onset of T1DM, duration of T1DM, DKA, hypoglycemia, nephropathy, neuropathy, retinopathy, macro-vascular complications, arthropathy, consanguinity, HbA1C or GAD65 autoantibodies. In conclusion, PTPN22 C1858T gene polymorphism is associated with development of T1DM in Egyptian pediatric population.

Keywords: Protein tyrosine phosphatase non-receptor type 22, T1DM, Lyp protein, Egyptian population.