title: PTPN22 R620W polymorphism in the ANCA-associated vasculitides.
abstract: OBJECTIVE
  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, χ(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, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73).
  
  
  CONCLUSIONS
  The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.
authors.affiliation: Dipartimento di Clinica Medica e Nefrologia, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.forename: Federica
authors.initials: F
authors.lastname: Maritati
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonatti
authors.forename: Federico
authors.initials: F
authors.lastname: Alberici
authors.forename: Elena
authors.initials: E
authors.lastname: Oliva
authors.forename: Paola
authors.initials: P
authors.lastname: Sebastio
authors.forename: Lucio
authors.initials: L
authors.lastname: Manenti
authors.forename: Rachele
authors.initials: R
authors.lastname: Brugnano
authors.forename: Maria G
authors.initials: MG
authors.lastname: Catanoso
authors.forename: Paolo
authors.initials: P
authors.lastname: Fraticelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Guida
authors.forename: Gina
authors.initials: G
authors.lastname: Gregorini
authors.forename: Stefano
authors.initials: S
authors.lastname: Possenti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Moroni
authors.forename: Antonio
authors.initials: A
authors.lastname: Leoni
authors.forename: Laura
authors.initials: L
authors.lastname: Pavone
authors.forename: Alberto
authors.initials: A
authors.lastname: Pesci
authors.forename: Renato A
authors.initials: RA
authors.lastname: Sinico
authors.forename: Lucafrancesco
authors.initials: L
authors.lastname: Di Toma
authors.forename: Marco
authors.initials: M
authors.lastname: D'Amico
authors.forename: Bruno
authors.initials: B
authors.lastname: Tumiati
authors.forename: Raffaele
authors.initials: R
authors.lastname: D'Ippolito
authors.forename: Carlo
authors.initials: C
authors.lastname: Buzio
authors.forename: Tauro M
authors.initials: TM
authors.lastname: Neri
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22