title: Functional variants of Fc gamma receptor (FCGR2A) and FCGR3A are not associated with susceptibility to systemic sclerosis in a large European Study (EUSTAR).
abstract: OBJECTIVE
  To investigate the possible role of FCGR2A 519A>G and FCGR3A 559A>C functional polymorphisms in the genetic predisposition to susceptibility to systemic sclerosis (SSc) or clinical phenotype.
  
  
  METHODS
  A total of 1566 patients with SSc and 2271 geographically matched controls were included in our study. We analyzed the genotype and allele frequencies of the FCGR2A 519A>G and FCGR3A 559A>C functional variants in 6 independent European cohorts of white patients with SSc, and white controls. The cohorts comprised 165 Dutch patients with SSc and 1326 controls, 236 Spanish patients with SSc and 257 controls, 267 German patients with SSc and 270 controls, 202 Swedish patients with SSc and 261 controls, 416 Italian patients with SSc and 157 controls, and additionally 280 English patients with SSc. Genotyping was performed using Taqman 5' allelic discrimination assay. The study reached a 99% power to detect the effect of a polymorphism at an OR of 1.3.
  
  
  RESULTS
  Neither FCGR2A 519A>G nor FCGR3A 559A>C was significantly associated with susceptibility to SSc. We did not find an association with specific disease phenotypes, limited or diffuse cutaneous involvement, autoantibody profiles, or pulmonary involvement.
  
  
  CONCLUSIONS
  Our study strongly suggests the lack of a role for the FCGR2A 519A>G and FCGR3A 559A>C polymorphisms in SSc susceptibility or clinical phenotype in 6 independent European cohorts.
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.forename: Jasper
authors.initials: J
authors.lastname: Broen
authors.forename: Blanca
authors.initials: B
authors.lastname: Rueda
authors.forename: Roger
authors.initials: R
authors.lastname: Hesselstrand
authors.forename: Dirk
authors.initials: D
authors.lastname: Wuttge
authors.forename: Carmen
authors.initials: C
authors.lastname: Simeon
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
authors.forename: Miguel
authors.initials: M
authors.lastname: Gonzalez-Gay
authors.forename: Anna
authors.initials: A
authors.lastname: Pros
authors.forename: Ariane
authors.initials: A
authors.lastname: Herrick
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Christopher
authors.initials: C
authors.lastname: Denton
authors.forename: Carmen
authors.initials: C
authors.lastname: Fonseca
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.forename: Madelon C
authors.initials: MC
authors.lastname: Vonk
authors.forename: Frank
authors.initials: F
authors.lastname: van den Hoogen
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: Rafaella
authors.initials: R
authors.lastname: Scorza
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.forename: Paolo
authors.initials: P
authors.lastname: Airó
authors.forename: Marieke
authors.initials: M
authors.lastname: Coenen
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
mesh_terms: D001323:Autoantibodies / Q000097:blood; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000097:blood / Q000235:genetics*; D045743:Scleroderma, Diffuse / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D045745:Scleroderma, Limited / Q000097:blood / Q000175:diagnosis / Q000235:genetics*
chemical_list: D001323:Autoantibodies; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG