Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

Abstract

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.

A Literature Review of Concomitant Primary Biliary Cirrhosis and GravesÂ’ Disease

“…On the other hand, possible non-HLA genes such as protein tyrosine phosphatase non-receptor type 22 (PTPN22), cytotoxic Tlymphocyte antigen 4 (CTLA4), and CD40 may influence the risk of developing GD [26,27]. Although some studies have reported that the PTPN22 polymorphism C1858T is associated with GD, it has not been observed to influence the risk of PBC in previous studies [28,29]. However, some studies have suggested that polymorphism in exon 1 of the CTLA-4 gene at position 49 (+49A/G, rs231775) may influence the risk of GD [27,30] and also the risk of PBC [31][32][33].…”

The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms

“…Data extraction was conducted as described previously [12]. Briefly, the following information was retrieved from each case-control study: author's name, year of publication, population of origin, frequency of genotypes, and alleles of each polymorphism in controls, PF + -and PF − -SSc patients.…”

Autoimmune Thyroid Diseases Concomitant with Crohn’s Disease and Ulcerative Colitis

“…The role of non-HLA genes such as PTPN22, CTLA4, and CD40 in GD patients has been extensively investigated [11]. Although some studies reported that PTPN22 does not influence the risk of IBD, including CD [12], other studies reported that PTPN22 may influence the risk of developing CD [13,14]. Moreover, some studies reported that CTLA4 may also influence the risk of developing CD [15,16].…”