ASSOCIATION OF PTPN22 AND TYPE 1 DIABETES MELLITUS

Abstract

Diabetes mellitus is a multifactorial metabolic disease and its etiology shows a significant genetic basis. Type 1 diabetes mellitus (T1DM) is most common chronic childhood disease. This autoimmune endocrine disease affects younger people and manifests itself most in puberty. It is characterized by degeneration of β cells of the endocrine pancreas, leading to insulin deficiency. Susceptibility gene polymorphisms in pathogenesis of type 1 diabetes and other autoimmune diseases have attracted a growing amount of attention in recent years. Among them, multiple studies have linked a single nucleotide polymorphism in the gene encoding the protein tyrosine phosphatase non-receptor type 22 (PTPN22) to T1DM. PTPN22 is expressed by many immune cells, such as T and B cells, monocytes, dendritic cells and NK cells. PTPN22 gene encodes lymphoid specific tyrosine phosphatase (LYP), an inhibitor of T cell activation. rs2476601 (R620W, 1858C→T) is one of the most studied LYP variations. This mutation results in partial or complete disruption of PTPN22 CSK (C-terminal Src kinase) binding. The C1858T polymorphism within this gene contributes to the development of T1DM because it reduces the activation of T lymphocytes. Many studies propose this SNP (single nucleotide polymorphism) as a considerable risk factor for T1DM among the Caucasian population. However, this research area shows a lot of potential for development of T1DM preventive treatments and even the prospective chance for application in screening tests, whereas T1DM patients with PTPN22 variant represent a promising target group for prevention trials with highly selective LYP inhibitors.