Publication type
Journal Article
Authors
Publication date
August 15, 2014
Summary:
Proteinase activated receptor-1 (PAR-1) plays a key role in mediating
the interplay between coagulation and inflammation in response to
injury. The aim of this study was to investigate the role of the
promoter SNP rs2227744G>A in modulating PAR-1/F2R gene
expression in the context of chronic obstructive pulmonary disease
(COPD) and COPD exacerbations. The function of the rs2227744G>A SNP
was investigated using reporter gene assays. The frequency of the
polymorphism in the UK population was assessed by genotyping 8579
healthy individuals from the Whitehall II and ELSA cohorts. The
rs2227744G>A SNP was genotyped in a carefully phenotyped cohort of
203 COPD cases and matched controls. The results were further replicated
in two different COPD cohorts. The minor allele of the rs2227744G>A
polymorphism was found to increase F2R expression by 2.6-fold
(p<0.001). The rs2227744G>A SNP was not significantly associated
with COPD, or with lung function, in all cohorts. The minor allele of
the SNP was found to be associated with protection from frequent
exacerbations (p=0.04) in the cohort of COPD patients for which
exacerbation frequency was available. Considering exacerbations as a
continuous variable, the presence of the minor allele was associated
with a significantly lower COPD exacerbation rate (3.03 vs 1.98
exacerbations/year, MWU p=0.04). Taken together these data do not
support a role for the rs2227744G>A F2R polymorphism in the
development of COPD but suggest a protective role for this polymorphism
from frequent exacerbations. Studies in separate cohorts to replicate
these findings are warranted.
Published in
American Journal of Physiology: Lung Cellular and Molecular Physiology
Volume
Volume: 307
DOI
http://dx.doi.org/10.1152/ajplung.00128.2014
ISSN
10400605
Subjects
Notes
Not held in Research Library - bibliographic reference only
Online in Albert Sloman Library, except current 12 months
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