The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism and Susceptibility to Autoimmune Diseases

Abstract

The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene located on chromosomes 1p 13.3-13 encodes a lymphoid-specific tyrosine phosphatase (Lyp) which is involved in autoimmunity by preventing spontaneous T-cell activation and T-cell development and inactivating T-cell receptor-associated kinases and their substrates. Several single nucleotide polymorphisms (SNPs) have been identified in PTPN22, but only one PTPN22 C1858T has been intensively studied in relation to autoimmune diseases. The PTPN22 C1858T functional polymorphism is a strong non-HLA risk factor for several autoimmune diseases and considered to play an important role in etiology of diseases due to significant production of autoantibodies. However, available literature on PTPN22 C1858T polymorphism and autoimmune diseases shows inconsistencies and ethnic variations. Therefore, further genetic studies on patients suffering from various autoimmune diseases from different ethnicities and PTPN22 gene polymorphisms are expected to help better understand the pathogenesis and will contribute to the development of more targeted therapies and biomarkers.

Genetic Polymorphism of PTPN22 in Autoimmune Diseases: A Comprehensive Review

“…A change in cytosine to thymidine at nucleotide 1858 resulted in a change in amino acids from arginine to tryptophan at codon 620 (R620W), and a change in the Lyp protein interrupts the cell signaling by disrupting the function of the T cell antigen receptor, mostly found in various types of lymphoid tissues. The Lyp protein is important in the prevention of spontaneous T cell activation, development, and inactivating of T-cell-receptor-associated kinases and their substrates [9]. Since Botinni et al first reported the association between PTPN22 gene variants and type 1 diabetes mellitus (T1DM), studies on other diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), autoimmune thyroid diseases, and vitiligo have been published successively.…”