Protein tyrosine phosphatase gene (PTPN22) polymorphism in multiple sclerosis.

Abstract

Alterations in the signalling pathway that regulate T-cell tyrosine phosphorylation play an important role in MS. Tyrosine phosphorylation is regulated by the equal and balanced action of protein tyrosine kinases and protein tyrosine phosphatases. The lymphoid-specific phosphatase (LYP), encoded by the PTPN22 gene, is important in negative control of T-cell activation and in T-cell development. A functional polymorphism at nucleotide 1858 in codon 620 (Arg620Trp) in the PTPN22 gene has been associated with type 1 diabetes mellitus (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in humans. In the present study, we tested the possible role of the 1858C→T variant of the PTPN22 gene in MS predisposition. We examined the distribution frequency of the PTPN22 1858C→T polymorphism of 120 patients with clinically defined MS and 200 healthy controls by a TaqMan 5’ allelic discrimination. The frequencies of 1858C/C, 1858C/T and 1858T/T genotypes were 87.5%%, 12% and 0.5% respectively in controls, and 83.3%, 15.8 % and 0.9 % in the patient group. The allele and genotype distribution frequencies were similar in MS patients and controls and were in Hardy-Weinberg equilibrium. This lack of association of the PTPN22 1858C→T polymorphism with MS should be interpreted cautiously. Because of the relatively small sample size, slight effects may be not uncovered and therefore these results do not completely rule out the possibility of an association with MS. The association of RA, T1D and SLE susceptibility with the PTPN22 1858C→T polymorphism suggests that the PTPN22 1858T allele predisposes individuals to developing autoimmune diseases. However, the PTPN22 1858C→T polymorphism seems not to be a critical point in the susceptibility to MS. Given the expression of this molecule in many immunological relevant cell types, our data support the hypothesis that PTPN22 may act in different ways in different autoimmune diseases.