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Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease.
Stankovic, Marija; Kojic, Snezana; Djordjevic, Valentina; Tomovic, Andrija; Nagorni-Obradovic, Ljudmila; Petrovic-Stanojevic, Natasa; Mitic-Milikic, Marija; Radojkovic, Dragica.
Afiliación
  • Stankovic M; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
  • Kojic S; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
  • Djordjevic V; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
  • Tomovic A; Oncology Region Europe, Novartis Pharma AG, Basel, Switzerland.
  • Nagorni-Obradovic L; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
  • Petrovic-Stanojevic N; Clinic of Pulmonology, Clinical Centre of Serbia, Belgrade, Serbia.
  • Mitic-Milikic M; Department of Pulmonology, Zvezdara University Medical Centre, Belgrade, Serbia.
  • Radojkovic D; School of Dentistry, Department of Internal Medicine, University of Belgrade, Belgrade, Serbia.
Environ Mol Mutagen ; 57(6): 447-54, 2016 07.
Article en En | MEDLINE | ID: mdl-27270564
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 < 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 < 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. © 2016 Wiley Periodicals, Inc.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Fumar / Regiones Promotoras Genéticas / Metaloproteinasa 9 de la Matriz / Enfermedad Pulmonar Obstructiva Crónica / Interacción Gen-Ambiente Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Environ Mol Mutagen Asunto de la revista: BIOLOGIA MOLECULAR / SAUDE AMBIENTAL Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Fumar / Regiones Promotoras Genéticas / Metaloproteinasa 9 de la Matriz / Enfermedad Pulmonar Obstructiva Crónica / Interacción Gen-Ambiente Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Environ Mol Mutagen Asunto de la revista: BIOLOGIA MOLECULAR / SAUDE AMBIENTAL Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos