title: Association of FCGR3A and FCGR3B copy number variations with systemic lupus erythematosus and rheumatoid arthritis in Taiwanese patients.
abstract: OBJECTIVE
  To determine whether copy number variations (CNVs) in FCGR3A and FCGR3B are associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese individuals.
  
  
  METHODS
  FCGR3A and FCGR3B CNV genotypes were determined in 846 patients with SLE, 948 patients with RA, and 1,420 healthy control subjects, using custom TaqMan CNV assays. The FCGR3A and FCGR3B CNV genotypes were compared between healthy control subjects and patients and among patients stratified according to clinical characteristics.
  
  
  RESULTS
  A low (<2) FCGR3A copy number was significantly associated with SLE (for <2 copies versus 2 copies, P = 5.06 × 10(-4) , false discovery rate-corrected P [PFDR ] = 0.001, odds ratio [OR] 3.26, 95% confidence interval [95% CI] 1.68-6.35) and RA (for <2 copies versus 2 copies, P = 5.83 × 10(-4) , PFDR = 0.0012, OR 2.82, 95% CI 1.56-5.1). A low FCGR3B copy number was also significantly associated with SLE (for <2 copies versus 2 copies, P = 0.0032, PFDR = 0.0032, OR 1.59, 95% CI 1.17-2.18). Notably, a high (>2) FCGR3A copy number was also associated with SLE (for >2 copies versus 2 copies, P = 0.003, PFDR = 0.0061, OR 1.6, 95% CI 1.17-2.18). Additionally, the FCGR3A low copy number genotype was significantly enriched in subsets of patients with SLE (those with ulcer, arthritis, rash, discoid rash, photosensitivity, nephritis, leukopenia, thrombocytopenia, depressed complement levels, and autoantibody positivity) and patients with RA (those positive for rheumatoid factor) compared with healthy control subjects. The FCGR3B low copy number genotype was also significantly enriched in SLE patients with ulcer, rash, discoid rash, photosensitivity, ascites, nephritis, complement level depression, and anti-double-stranded DNA antibody positivity compared with control subjects. However, FCGR3B CNVs were not associated with RA susceptibility (for <2 copy numbers versus 2 copy numbers, P = 0.3584, OR 1.15, 95% CI 0.85-1.55) and clinical characteristics.
  
  
  CONCLUSIONS
  In Taiwanese individuals, a low FCGR3A copy number is a common risk factor for SLE and RA, while a low FCGR3B copy number confers a risk of SLE but not RA.
authors.affiliation: Chang Gung University College of Medicine, Taiwan, Republic of China.
authors.forename: Ji-Yih
authors.initials: JY
authors.lastname: Chen
authors.forename: Chin-Man
authors.initials: CM
authors.lastname: Wang
authors.forename: Su-Wei
authors.initials: SW
authors.lastname: Chang
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Cheng
authors.forename: Yeong-Jian Jan
authors.initials: YJ
authors.lastname: Wu
authors.forename: Jing-Chi
authors.initials: JC
authors.lastname: Lin
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Huei-Huang
authors.initials: HH
authors.lastname: Ho
authors.forename: Jianming
authors.initials: J
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics*; D012213:Rheumatic Fever / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: C496124:FCGR3A protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG