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Volume 2 Environment Pollution and Climate Change
ISSN: 2573-458X Climate Change 2018 &
Global ENVITOX 2018
October 04-06, 2018
October 04-06, 2018
London, UK
16th Annual Meeting on
Environmental Toxicology and Biological Systems
&
5th World Conference on Climate Change
JOINT EVENT
MMP9 in lung disorders: Identification and analysis of gene-environment interaction between the
MMP9 C–1562T variant and cigarette smoke in the occurrence and severity of COPD
Marija M Stankovic
The Institute of Molecular Genetics and Genetic Engineering—University of Belgrade, Serbia
MMP9 is an elastolytic enzyme, the expression and activity of which are tightly regulated. In healthy lungs, MMP9 is
not expressed, but in response to inflammatory cytokines, pulmonary and immune cells may secrete MMP9. The
deregulation of MMP9 is implicated in various lung disorders, e.g. chronic obstructive pulmonary disease (COPD), asthma,
bronchiectasis, cystic fibrosis (CF), carcinoma, etc. Accordingly, understanding the effect of environmental factors on MMP9
expression in lungs is of great importance. Cigarette smoke, infections, LPS and chemical agents increase the production of
MMP9. Besides, genetic factors such as MMP9 C–1562T (rs3918242) functional variant, has been recognized as a risk in
several disorders, but its role in COPD is controversial. Herein, results about the identification and functional assessment of
gene-environment interaction between the MMP9 C–1562T variant and cigarette smoke in the pathogenesis of COPD are
presented. Interaction between the C–1562T variant and cigarette smoking was analyzed using a case-control model. The
effect of CSC on MMP9 expression and activity was determined by real-time PCR and gelatine zymography. The response of
the C–1562T promoter variant to CSC was examined using a dual luciferase reporter assay. The frequency of T allele carriers
was higher in COPD group than in smoker controls (P=0.027). Interaction between the T allele and cigarette smoking was
identified in COPD occurrence (P=0.005) and severity (P=0.001). Expression of MMP9 mRNA and pro-MMP9 gelatinolytic
activity were dose-dependent (p<0.01, p<0.05). A functional analysis of the C–1562T variant demonstrated a dose-dependent
and allele specific response (P<0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found
for the promoter harbouring the T allele compared to the promoter harbouring the C allele (P<0.05). Our study is the first
to reveal an interaction between the MMP9–1562T allele and cigarette smoke in COPD, emphasising gene-environment
interactions in complex lung disorders, such as COPD.
Environ Pollut Climate Change 2018, Volume 2
DOI: 10.4172/2573-458X-C1-003