期刊
RESPIRATION
卷 81, 期 2, 页码 142-149出版社
KARGER
DOI: 10.1159/000321997
关键词
Copy number variation; Fc receptors; Gene dosage; Idiopathic pulmonary fibrosis; Neutrophils
资金
- British Heart Foundation [FS/05/119/19568]
- MRC [G0901697, G108/460] Funding Source: UKRI
- Medical Research Council [G9900991B, G108/460, G0901697] Funding Source: researchfish
Background: Several genes exhibit copy number variation (CNV), including FCGR3B which encodes the IgG receptor Fc gamma RIIIb. Engagement of Fc gamma 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; chi(2) = 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 Fc gamma receptors in IPF disease pathogenesis. Copyright (C) 2010 S. Karger AG, Basel
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