Yali Cao1, Kuo Liu2, Zhigang Tian2, Susan L Hogan2, Jiajin Yang2, Caroline J Poulton2, Ronald J Falk2, Wenge Li2. 1. From the Department of Nephrology, China-Japan Friendship Hospital; Emergency Department, China MeiTan General Hospital, National Mining Medical Center; Department of Surgery, Beijing LuHe Hospital, Beijing, China; Division of Nephrology and Hypertension, University of North Carolina (UNC) Kidney Center, Department of Medicine, UNC at Chapel Hill, Chapel Hill, North Carolina, USA.Y. Cao, MD, PhD, Department of Nephrology, China-Japan Friendship Hospital; K. Liu, MD, PhD, Emergency Department, China MeiTan General Hospital, National Mining Medical Center; Z. Tian, MD, Department of Surgery, Beijing LuHe Hospital; S.L. Hogan, MPH, PhD; J. Yang, MD; C.J. Poulton, MSW; R.J. Falk, MD, UNC Kidney Center, Department of Medicine, UNC at Chapel Hill; W. Li, MD, PhD, Department of Nephrology, China-Japan Friendship Hospital. yalicao050501@hotmail.com. 2. From the Department of Nephrology, China-Japan Friendship Hospital; Emergency Department, China MeiTan General Hospital, National Mining Medical Center; Department of Surgery, Beijing LuHe Hospital, Beijing, China; Division of Nephrology and Hypertension, University of North Carolina (UNC) Kidney Center, Department of Medicine, UNC at Chapel Hill, Chapel Hill, North Carolina, USA.Y. Cao, MD, PhD, Department of Nephrology, China-Japan Friendship Hospital; K. Liu, MD, PhD, Emergency Department, China MeiTan General Hospital, National Mining Medical Center; Z. Tian, MD, Department of Surgery, Beijing LuHe Hospital; S.L. Hogan, MPH, PhD; J. Yang, MD; C.J. Poulton, MSW; R.J. Falk, MD, UNC Kidney Center, Department of Medicine, UNC at Chapel Hill; W. Li, MD, PhD, Department of Nephrology, China-Japan Friendship Hospital.
Abstract
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.
OBJECTIVE: No clear consensus has been reached on the PTPN22R620W polymorphism and anti-neutrophil cytoplasmic antibody (ANCA) disease, especially when stratified by ANCA specificity and disease phenotypes. METHODS: A metaanalysis was conducted on the PTPN22R620W 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.
Entities:
Keywords:
ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; GRANULOMATOSIS WITH POLYANGIITIS; MICROSCOPIC POLYANGIITIS; MYELOPEROXIDASE; PROTEIN TYROSINE PHOSPHATASE NONRECEPTOR 22; PROTEINASE 3
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