Functional Variants of Fc Gamma Receptor (FCGR2A) and FCGR3A Are Not Associated with Susceptibility to Systemic Sclerosis in a Large European Study (EUSTAR)

Behrooz Z. Alizadeh, Jasper Broen, Blanca Rueda, Roger Hesselstrand, Dirk Wuttge, Carmen Simeon, Norberto Ortego-Centeno, Miguel A. Gonzalez-Gay, Anna Pros, Ariane Herrick, Jane Worthington, Christopher Denton, Carmen Fonseca, Gabriela Riemekasten, Madelon C. Vonk, Frank Van den Hoogen, Serena Guiducci, Marco Matucci-Cerinic, Rafaella Scorza, Lorenzo BerettaPaolo Airo, Marieke Coenen, Javier Martin, Bobby P. C. Koeleman, Timothy R. D. J. Radstake*, EUSTAR

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

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.

Conclusion. 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. (First Release June 15 2010; J Rheumatol 2010;37:1673-9; doi:10.3899/jrheum.091259)

Original languageEnglish
Pages (from-to)1673-1679
Number of pages7
JournalThe Journal of Rheumatology
Volume37
Issue number8
DOIs
Publication statusPublished - 1-Aug-2010
Externally publishedYes

Keywords

  • Autoantibodies
  • Europe
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, IgG
  • Scleroderma, Diffuse
  • Scleroderma, Limited

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