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Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression

Alexander, Karen M.; Wallace, William A; Murchison, John T.; Hart, Simon P.; Bournazos, Stylianos; Grinfeld, Jacob; Alexander, Karen M; Murchison, John T; Wallace, William A.; McFarlane, Pauline; Hirani, Nikhil; Simpson, A. John; Dransfield, Ian; Hart, Simon P

Authors

Karen M. Alexander

William A Wallace

John T. Murchison

Simon P. Hart

Stylianos Bournazos

Jacob Grinfeld

Karen M Alexander

John T Murchison

William A. Wallace

Pauline McFarlane

Nikhil Hirani

A. John Simpson

Ian Dransfield

Simon P Hart S.Hart@hull.ac.uk



Abstract

Background: A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF). The R131H (rs1801274) polymorphism of the IgG receptor FcγRIIa determines receptor affinity for IgG subclasses and is associated with several chronic inflammatory diseases. We investigated whether this polymorphism is associated with IPF susceptibility or progression.Methods: In a case-control study, we compared the distribution of FcγRIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification.Results: No differences in the frequency of FcγRIIa genotypes were evident between IPF patients and control subjects. However, significantly impaired pulmonary function at diagnosis was observed in HH compared to RR homozygotes, with evidence of more severe restriction (reduced forced vital capacity (FVC)) and lower diffusing capacity for carbon monoxide (DL CO ). Similarly, increased frequency of the H131 allele was observed in patients with severe disease (DL CO < 40% predicted) (0.53 vs. 0.38; p = 0.03). Furthermore, the H131 allele was associated with progressive pulmonary fibrosis as determined by > 10% drop in FVC and/or > 15% fall in DL CO at 12 months after baseline (0.48 vs. 0.33; p = 0.023).Conclusions: These findings support an association between the FcγRIIa R131H polymorphism and IPF severity and progression, supporting the involvement of immunological mechanisms in IPF pathogenesis. © 2010 Bournazos et al; licensee BioMed Central Ltd.

Journal Article Type Article
Publication Date Oct 7, 2010
Journal BMC.Pulm.Med.
Electronic ISSN 1471-2466
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 10
Issue 1
Article Number ARTN 51
APA6 Citation Bournazos, S., Grinfeld, J., Alexander, K. M., Murchison, J. T., Wallace, W. A., McFarlane, P., …Hart, S. P. (2010). Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression. BMC Pulmonary Medicine, 10(1), doi:10.1186/1471-2466-10-51
DOI https://doi.org/10.1186/1471-2466-10-51
Keywords Association; CAPACITY; diagnosis; Disease; Genotype; Idiopathic Pulmonary Fibrosis; Inflammation; methods; Patients; Research; Research Support

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Copyright Statement
© 2010 Bournazos et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.



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