title: PTPN22 R620W polymorphism and ANCA disease risk in white populations: a metaanalysis.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Yali
authors.initials: Y
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Kuo
authors.initials: K
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hogan
authors.affiliation: 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.
authors.forename: Jiajin
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Poulton
authors.affiliation: 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.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Falk
authors.affiliation: 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.
authors.forename: Wenge
authors.initials: W
authors.lastname: Li
mesh_terms: D000483:Alleles; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics* / Q000276:immunology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; GRANULOMATOSIS WITH POLYANGIITIS; MICROSCOPIC POLYANGIITIS; MYELOPEROXIDASE; PROTEIN TYROSINE PHOSPHATASE NONRECEPTOR 22; PROTEINASE 3