Objective: Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where several genes have been associated with the disease. While the major histocompatibility complex has been shown to be the major locus, contributions of other loci in different combinations seem to have synergistic effects. PTPN22 (Protein tyrosine phosphatase non-receptor, type 22) gene encoding lymphoid tyrosine phosphatase (LYP) is a negative regulator of T cell signaling. A gain of function mutant at nucleotide position 1858 C>T has been associated with diabetes, however, it is reported to be absent in Asians. We have studied PTPN22 C1858T polymorphism in T1D patients from North India since there are no reports from this region.
Methods: PTPN22 C1858T polymorphism was studied in 250 T1D patients and 480 healthy controls using polymerase chain reaction followed by restriction digestion (PCR-RFLP). Alleles of HLA-DRB1 locus were studied using PCR followed by hybridization with sequence specific oligonucleotide probes using a bead based assay on Luminex platform.
Results: In spite of reports of absence of 1858T allele in Asians, we observed this allele to be present in North Indians, albeit with low frequency (1.98%). However, T1D patients from the same ethnic background showed significantly higher frequency of the allele and heterozygous genotype 1858CT as compared to controls. Patients with both 1858CT and 1858CC genotypes had predisposing MHC alleles.
Conclusion: The association of PTPN22 1858CT genotype with Type 1 diabetes was independent of the predisposing Human leukocyte antigen (HLA) alleles DRB1*03:01, DRB1*04:01, DRB1*04:05 in North Indian patients, suggesting their integrated roles in manifestation of T1D. Based on the reported role of PTPN22 1858CT genotype in defective innate immune responses against viral infections, and defects in early T cell signaling, it is tempting to speculate that it may be detrimental for the destruction of pancreatic beta cells in the present scenario.