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Impact of Allele Copy Number of Polymorphisms in FCGR3A and FCGR3B Genes on Susceptibility to Ulcerative Colitis

Asano, Kouichi MD*,†; Matsumoto, Takayuki MD*; Umeno, Junji MD*; Hirano, Atsushi MD*,‡; Esaki, Motohiro MD*; Hosono, Naoya PhD; Matsui, Toshiyuki MD§; Kiyohara, Yutaka MD; Nakamura, Yusuke MD; Kubo, Michiaki MD*,‡; Kitazono, Takanari MD*

doi: 10.1097/MIB.0b013e318298118e
Original Basic Science Articles

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 × 10−9).

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.

Article first published online 2 August 2013

Departments of *Medicine and Clinical Science, Graduate School of Medical Sciences, and

Endoscopic Diagnosis and Therapeutics, Kyushu University Hospital, Fukuoka, Japan;

Laboratory for Genotyping Development, RIKEN Center for Genomic Medicine, Kanagawa, Japan;

§Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan;

Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Reprints: Kouichi Asano, MD, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582 Fukuoka, Japan (e-mail: k-asano@intmed2.med.kyuishu-u.ac.jp).

Supported in part by the Ministry of Education, Culture, Sports, Science and Technology.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

Received April 10, 2013

Accepted April 21, 2013

© Crohn's & Colitis Foundation of America, Inc.
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