Objective: No clear consensus has been reached on the PTPN22 R620W polymorphism and anti-neutrophil cytoplasmic antibody (ANCA) disease, especially when stratified by ANCA specificity and disease phenotypes.
Methods: A metaanalysis was conducted on the PTPN22 R620W polymorphism across 4 studies in 1399 white patients with ANCA disease and 9934 normal control subjects.
Results: Overall, metaanalysis showed a statistically significant association between the A allele and ANCA disease in all subjects (OR 1.44, 95% CI 1.26-1.64, p < 0.00001), and stratification by disease category indicated the A allele was associated with granulomatosis with polyangiitis (Wegener's; GPA; OR 1.72, 95% CI 1.35-2.20, p < 0.0001) and microscopic polyangiitis (MPA; OR 1.53, 95% CI 1.08-2.15, p = 0.02) as compared to controls. However, when stratified by ANCA specificity, the association of the A allele was statistically evident among those with proteinase 3 (PR3) ANCA disease (OR 1.74, 95% CI 1.25-2.430, p = 0.001), with the same trend but not statistically associated with myeloperoxidase ANCA disease (OR 1.94, 95% CI 0.64-5.85, p = 0.24). The marked associations were also demonstrated between this allele with lung (OR 1.69, 95% CI 1.21-2.36, p = 0.002), ENT (OR 2.03, 95% CI 1.45-2.84, p < 0.0001), skin (OR 2.55, 95% CI 1.69-3.84, p < 0.0001), and peripheral neuropathy involvement (OR 2.12, 95% CI 1.39-3.22, p = 0.0005).
Conclusion: The PTPN22 620W allele confers susceptibility to the occurrence and development of ANCA disease in whites, with specific evidence among subsets with GPA, MPA, and PR3 ANCA.
Keywords: ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; GRANULOMATOSIS WITH POLYANGIITIS; MICROSCOPIC POLYANGIITIS; MYELOPEROXIDASE; PROTEIN TYROSINE PHOSPHATASE NONRECEPTOR 22; PROTEINASE 3.