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Copy number variation of FCGR3B is associated with susceptibility to idiopathic pulmonary fibrosis

Hart, Simon; Bournazos, Stylianos; Bournazou, Irini; Murchison, John T.; Wallace, William A.; McFarlane, Pauline; Hirani, Nikhil; Simpson, A. John; Dransfield, Ian; Hart, Simon P.

Authors

Simon Hart S.Hart@hull.ac.uk

Stylianos Bournazos

Irini Bournazou

John T. Murchison

William A. Wallace

Pauline McFarlane

Nikhil Hirani

A. John Simpson

Ian Dransfield

Simon P. Hart



Abstract

Background: Several genes exhibit copy number variation (CNV), including FCGR3B which encodes the IgG receptor FcγRIIIb. Engagement of Fcγ receptors by IgG complexes may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Objectives: To investigate whether FCGR3B CNV is associated with susceptibility to IPF. Methods: In a case-control study we compared FCGR3B copy number in 142 patients with IPF and in 221 controls by real-time quantitative PCR using CD36 as gene copy control. Results: Significantly increased FCGR3B:CD36 ratio was evident in the IPF cohort compared to controls (p = 0.009). Association of FCGR3B copy number with IPF susceptibility was further confirmed by a likelihood ratio statistical approach (p = 0.003). FCGR3B copy number assignment based on FCGR3B:CD36 ratios revealed significant skewing in the distribution of FCGR3B copy number between IPF patients and controls. In the IPF cohort, there was increased frequency of >2 FCGR3B copies compared to controls (0.30 vs. 0.19; χ2 = 9.27; d.f. 2; p = 0.0097). The presence of >2 FCGR3B copies was associated with higher risk of IPF (p = 0.01, OR: 1.914, 95% CI: 1.17–3.12). Conclusions: These findings support an association of FCGR3B copy number with susceptibility to IPF and propose a novel role for Fcγ receptors in IPF disease pathogenesis.

Journal Article Type Article
Publication Date 2011-02
Journal RESPIRATION
Print ISSN 0025-7931
Electronic ISSN 1423-0356
Publisher Karger Publishers
Peer Reviewed Peer Reviewed
Volume 81
Issue 2
Pages 142-149
APA6 Citation Bournazos, S., Bournazou, I., Murchison, J. T., Wallace, W. A., McFarlane, P., Hirani, N., …Hart, S. P. (2011). Copy number variation of FCGR3B is associated with susceptibility to idiopathic pulmonary fibrosis. Respiration, 81(2), 142-149. doi:10.1159/000321997
DOI https://doi.org/10.1159/000321997
Keywords Copy number variation; Fc receptors; Gene dosage; Idiopathic pulmonary fibrosis; Neutrophils
Publisher URL https://www.karger.com/Article/FullText/321997
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