Association analysis of the 1858C>T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases

Abstract

A functional single nucleotide polymorphism, 1858C4T, in the PTPN22 gene, encoding a tyrosine phosphatase, has been reported to be associated with type I diabetes and some other autoimmune diseases. To further investigate whether this polymorphism may be a general susceptibility factor for autoimmunity, we performed an association study in five different autoimmune diseases, three previously not tested. We found an association with juvenile idiopathic arthritis (OR ¼ 1.41; P ¼ 0.04), not previously reported, and a tendency for an association with coeliac disease (OR ¼ 1.35; P ¼ 0.08). In primary sclerosing cholangitis, no association was observed (OR ¼ 0.95; P ¼ 0.8). Furthermore, we confirmed the increased risk in rheumatoid arthritis (OR ¼ 1.58; P ¼ 0.001), but could not find support for an association with systemic lupus erythematosus (OR ¼ 0.94; P ¼ 0.8). Altogether, we have provided further evidence of an association between autoimmune diseases and the 1858C4T polymorphism in PTPN22.

Linkage proof for PTPN22 , a rheumatoid arthritis susceptibility gene and a human autoimmunity gene

“…The few positive reports of an association with RF Ϫ RA, in view of the vast majority of negative reports, might be false positives, as suggested by the clear negative linkage findings in our study (13). There were association reports for one form of idiopathic juvenile arthritis, but a well powered negative linkage study raised serious doubts on the reality of the association (28,(34)(35)(36).…”

Finnish case–control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis

“…These JIA results do not support the findings of a previous study, which suggested that the PTPN22 1858T allele variant is associated with this disease. 9 However, the relatively small sample size (230 probands in the current study) does not preclude a modest effect from this gene in Finnish JIA. Differences in results between the current study and the previous study performed in Norwegian subjects may also be explained by differences between populations or the possibility of hidden population structure that was not controlled for in the previous study.…”

“…The identification of PTPN22 1858 C/T as a putative disease risk allele in type 1 diabetes (T1D) [1][2][3][4][5][6] and subsequently RA [7][8][9] and other autoimmune diseases including SLE, 10,11 Graves disease 12 and JIA 9 has engendered considerable excitement. 13 PTPN22 also known as LYP (lymphocyte phosphatase) encodes a hematopoietic tissue-specific protein tyrosine phosphatase that is thought to inhibit T-cell activation through its association with the Csk tyrosine kinase.…”

TCR-induced downregulation of protein tyrosine phosphatase PEST augments secondary T cell responses

“…Finally, since a single-nucleotide polymorphism in position 1858 in PTPN22 (that encodes LYP) has been found to predispose carriers to multiple autoimmune diseases (Bottini et al, 2004;Smyth et al, 2004;Begovich et al, 2004;Viken et al, 2005;Kyogoku et al, 2004;Vang et al, 2005;reviewed in Bottini et al, 2006), it seems quite possible that similar variants of PTP-PEST may be involved in immunological disease (Mustelin, 2006). It is therefore important to clarify the regulation and physiological functions of these phosphatases in T lymphocytes and other immune cells.…”