title: Role of the Fcgamma receptor IIA polymorphism in the antiphospholipid syndrome: an international meta-analysis.
abstract: OBJECTIVE
  To assess the impact of the FcgammaRIIA-R/H131 polymorphism on the risk for antiphospholipid syndrome (APS), both primary and secondary to systemic lupus erythematosus (SLE).
  
  
  METHODS
  This international meta-analysis combined data from 9 research teams. FcgammaRIIA-R/H131 genotypes were determined in 481 APS cases (206 with primary APS), 1,420 SLE controls, and 1,655 disease-free controls. Data were combined using fixed-effects and random-effects models.
  
  
  RESULTS
  Compared with disease-free controls, the RR genotype was enriched in the entire group of APS cases (odds ratio [OR] 1.65, 95% confidence interval [95% CI] 1.28-2.14); this was driven mostly by patients with secondary APS (OR 1.95, 95% CI 1.45-2.63). The excess of RR homozygotes but not heterozygotes among APS patients suggested a recessive mode of inheritance, rather than the additive model seen for SLE susceptibility, where RR conferred greatest risk, and RH intermediate risk, for SLE. This probably reflected the additional influence of another opposing genetic effect of HH homozygosity on APS predisposition (OR 0.72 for RH versus HH, 95% CI 0.55-0.96). Among SLE patients, those with APS were more frequently HH homozygotes than heterozygotes (OR 0.56 for RH versus HH, 95% CI 0.39-0.81). HH homozygosity also tended to predominate in primary APS compared with secondary APS (OR 0.50 for RR versus HH, 95% CI 0.25-0.99 by fixed-effects model). There was no significant between-study heterogeneity for any of these effects.
  
  
  CONCLUSIONS
  The FcgammaRIIA-R/H131 polymorphism is an important determinant of predisposition to APS, with different influences on SLE and APS susceptibility per se.
authors.affiliation: University of Ioannina School of Medicine, Ioannina, Greece.
authors.forename: Fotini B
authors.initials: FB
authors.lastname: Karassa
authors.forename: Marc
authors.initials: M
authors.lastname: Bijl
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Davies
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Munther A
authors.initials: MA
authors.lastname: Khamashta
authors.forename: Karin
authors.initials: K
authors.lastname: Manger
authors.forename: Marc
authors.initials: M
authors.lastname: Michel
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Jane E
authors.initials: JE
authors.lastname: Salmon
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Yoo
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D016736:Antiphospholipid Syndrome / Q000453:epidemiology* / Q000235:genetics*; D015982:Bias; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG