PTPN22 R620W polymorphism in the ANCA-associated vasculitides

Objectives. PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism ( SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. Methods. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. Results. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, chi(2) = 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, chi(2) = 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, chi(2) = 7.258, OR = 1.98), lung involvement (P = 0.0060, chi(2) = 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, chi(2) = 16.567, OR = 3.73). Conclusion. The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.