title: Impact of allele copy number of polymorphisms in FCGR3A and FCGR3B genes on susceptibility to ulcerative colitis.
abstract: BACKGROUND
  Polymorphisms in the Fcγ receptor genes have been implicated in several autoimmune diseases, including ulcerative colitis (UC). However, most of these reports had not taken into account the effect of copy number variation at this region.
  
  
  METHODS
  We investigated the combined effect of allele and gene copy number of FCGR3A-158F/V and FCGR3B-NA1/NA2 on susceptibility to UC. Study subjects were composed of a total of 752 Japanese patients with UC and 2062 Japanese control subjects. To estimate allele copy number of the 2 polymorphisms, we integrated the results of PCR-based real-time Invader assay (PCR-RETINA) that measures the allelic ratio and Taqman assay that detects the total copy number. We analyzed the associations of allele copy number with UC using logistic regression model.
  
  
  RESULTS
  Gene and allele copy numbers of FCGR3A and FCGR3B were successfully determined in more than 99.5% of the study subjects. Allele copy number of FCGR3A-158F/V demonstrated significant association with susceptibility to UC (P = 0.02), although each single-nucleotide polymorphism and copy number variation alone did not show significant association. Although allele copy number of FCGR3B-NA1/NA2 (P = 0.002) also showed significant association with UC susceptibility, this association seemed to reflect the effect of FCGR3B gene copy number. Subsequent haplotype analyses revealed a strong association of a haplotype FCGR2A-131H/R and copy number of FCGR3B gene (P = 6.5 × 10).
  
  
  CONCLUSIONS
  Allele copy number of FCGR3A-158F/V and FCGR3B gene copy number were associated with UC susceptibility. Our results suggest that organizing handling of immune complex by FCGR3A, FCGR3B, and FCGR2A may play a crucial role in the pathogenesis of UC.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan. k-asano@intmed2.med.kyuishu-u.ac.jp
authors.forename: Kouichi
authors.initials: K
authors.lastname: Asano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Junji
authors.initials: J
authors.lastname: Umeno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirano
authors.forename: Motohiro
authors.initials: M
authors.lastname: Esaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsui
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: C496124:FCGR3A protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D004247:DNA