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


OBJECTIVE
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; χ(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 Fcγ receptors in IPF disease pathogenesis.
University of Edinburgh, Medical Research Council Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK. s.bournazos@sms.ed.ac.uk
Stylianos
S
Bournazos
Irini
I
Bournazou
John T
JT
Murchison
William A
WA
Wallace
Pauline
P
McFarlane
Nikhil
N
Hirani
A John
AJ
Simpson
Ian
I
Dransfield
Simon P
SP
Hart
D000368:Aged; D000369:Aged, 80 and over; D056915:DNA Copy Number Variations; D018450:Disease Progression; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism
C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG