Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease
Authorized Users Only
2016
Authors
Stanković, MarijaKojić, Snežana

Đorđević, Valentina
Tomović, Andrija
Nagorni-Obradović, Ljudmila
Petrović-Stanojević, Nataša
Mitic-Milikić, Marija
Radojković, Dragica

Article (Published version)

Metadata
Show full item recordAbstract
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 cigaret...te 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.
Keywords:
lung disease / MMP9 / cigarette smoke / gene-environment interactionSource:
Environmental & Molecular Mutagenesis, 2016, 57, 6, 447-454Publisher:
- Wiley, Hoboken
Funding / projects:
DOI: 10.1002/em.22025
ISSN: 0893-6692
PubMed: 27270564
WoS: 000379953300003
Scopus: 2-s2.0-84978863694
Collections
Institution/Community
Stomatološki fakultetTY - JOUR AU - Stanković, Marija AU - Kojić, Snežana AU - Đorđević, Valentina AU - Tomović, Andrija AU - Nagorni-Obradović, Ljudmila AU - Petrović-Stanojević, Nataša AU - Mitic-Milikić, Marija AU - Radojković, Dragica PY - 2016 UR - https://smile.stomf.bg.ac.rs/handle/123456789/2089 AB - 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. PB - Wiley, Hoboken T2 - Environmental & Molecular Mutagenesis T1 - Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease VL - 57 IS - 6 SP - 447 EP - 454 DO - 10.1002/em.22025 ER -
@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" }
Stanković, M., Kojić, S., Đorđević, V., Tomović, A., Nagorni-Obradović, L., Petrović-Stanojević, N., Mitic-Milikić, M.,& Radojković, D.. (2016). Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease. in Environmental & Molecular Mutagenesis Wiley, Hoboken., 57(6), 447-454. https://doi.org/10.1002/em.22025
Stanković M, Kojić S, Đorđević V, Tomović A, Nagorni-Obradović L, Petrović-Stanojević N, Mitic-Milikić M, Radojković D. Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease. in Environmental & Molecular Mutagenesis. 2016;57(6):447-454. doi:10.1002/em.22025 .
Stanković, Marija, Kojić, Snežana, Đorđević, Valentina, Tomović, Andrija, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Mitic-Milikić, Marija, Radojković, Dragica, "Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease" in Environmental & Molecular Mutagenesis, 57, no. 6 (2016):447-454, https://doi.org/10.1002/em.22025 . .