@article{
author = "Stanković, Marija and Kojić, Snežana and Đorđević, Valentina and Tomović, Andrija and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Mitic-Milikić, Marija and Radojković, Dragica",
year = "2016",
abstract = "The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR=2.7, P=0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR=4.38, P=0.005) and severity (P=0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P lt 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P lt 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 as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016.",
publisher = "Wiley, Hoboken",
journal = "Environmental & Molecular Mutagenesis",
title = "Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease",
volume = "57",
number = "6",
pages = "447-454",
doi = "10.1002/em.22025"
}