Functional variants of Fc gamma receptor (FCGR2A) and FCGR3A are not associated with susceptibility to systemic sclerosis in a large European Study (EUSTAR).
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.
Alizadeh
Behrooz Z
BZ
Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Broen
Jasper
J
Rueda
Blanca
B
Hesselstrand
Roger
R
Wuttge
Dirk
D
Simeon
Carmen
C
Ortego-Centeno
Norberto
N
Gonzalez-Gay
Miguel A
MA
Gonzalez-Gay
Miguel
M
Pros
Anna
A
Herrick
Ariane
A
Worthington
Jane
J
Denton
Christopher
C
Fonseca
Carmen
C
Riemekasten
Gabriela
G
Vonk
Madelon C
MC
van den Hoogen
Frank
F
Guiducci
Serena
S
Matucci-Cerinic
Marco
M
Scorza
Rafaella
R
Beretta
Lorenzo
L
Airó
Paolo
P
Coenen
Marieke
M
Martin
Javier
J
Koeleman
Bobby P C
BP
Radstake
Timothy R D J
TR
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*
D001323:Autoantibodies; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG