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.

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.

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. https://doi.org/10.1159/000321997

• Journal Article Type: Article
• Acceptance Date: Oct 2, 2010
• Online Publication Date: Nov 27, 2010
• 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
• DOI: https://doi.org/10.1159/000321997
• Keywords: Copy number variation; Fc receptors; Gene dosage; Idiopathic pulmonary fibrosis; Neutrophils
• Public URL: https://hull-repository.worktribe.com/output/417789
• Publisher URL: https://www.karger.com/Article/FullText/321997