PTPN22 1858C>T Polymorphism Distribution in Europe and Association with Rheumatoid Arthritis: Case-Control Study and Meta-Analysis

Abstract

ObjectiveThe PTPN22 rs2476601 polymorphism is associated with rheumatoid arthritis (RA); nonetheless, the association is weaker or absent in some southern European populations. The aim of the study was to evaluate the association between the PTPN22 rs2476601 polymorphism and RA in Italian subjects and to compare our results with those of other European countries, carrying out a meta-analysis of European data.MethodsA total of 396 RA cases and 477 controls, all of Italic ancestry, were genotyped for PTPN22 rs2476601 polymorphism. Patients were tested for autoantibodies positivity. The meta-analysis was performed on 23 selected studies.ResultsThe PTPN22 T1858 allele was significantly more frequent in RA patients compared to controls (5.7% vs. 3.7%, p = 0.045). No clear relationship arose with the autoantibodies tested. The 1858T allele frequency in Italian RA patients was lower than the one described in northern European populations and similar to the frequency found in Spain, Turkey, Greece, Tunisia. A clear-cut North-South gradient arose from the analysis.ConclusionsThe PTPN22 T1858 allele is associated with RA in the Italian population. A North-South gradient of the allele frequency seems to exist in Europe, with a lower prevalence of the mutation in the Mediterranean area.

Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis

“…We report in the present study association of PTPN22 1858C→T polymorphism with susceptibility to RA among Egyptian patients, which is consistent with previous studies done on different ethnic populations such as on Iranian population [20], Italian [21] and Mexican population [22].…”

Overexpression of the autoimmunity-associated phosphatase PTPN22 promotes survival of antigen-stimulated CLL cells by selectively activating AKT

“…The PTPN22 R620W autoimmunedisease risk allele was also detected in only 1 case (3.4%), consistent with the expected frequency of this allele for the same healthy population (3.7%). 31 Another less frequent PTPN22 variant (R263Q), which has been associated with reduced risk for autoimmune disease, was observed in another patient. 32 Overall, the sequencing analysis revealed that PTPN22 and SHP-1 are not frequently mutated in CLL and that the PTPN22 autoimmunedisease risk variant is not more prevalent in CLL patients than in the general population.…”

The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico

“…Likewise, loss of tolerance to self-antigens, which leads to stimulation of lymphocytes and other immune cells, release of cytokines, activation of complement and the production of autoantibodies, contributes to the pathogenesis of the RA [5]. Genetic factors are thought to be responsible for up 50-60% of the predisposition to RA [6]. The +1858C/T (rs2476601) single-nucleotide polymorphism (SNP) in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene has been associated with susceptibility to multiple autoimmune diseases [3,6].…”

“…Genetic factors are thought to be responsible for up 50-60% of the predisposition to RA [6]. The +1858C/T (rs2476601) single-nucleotide polymorphism (SNP) in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene has been associated with susceptibility to multiple autoimmune diseases [3,6]. The human PTPN22 gene, is located on chromosome 1p13, and encodes a lymphoid protein tyrosine phosphatase (LYP), which is important in negative control of T cell activation and in T cell development.…”