Genetic susceptibility to asbestos-related fibrotic pleuropulmonary changes
| Autor: | S. Hämäläinen, Harri Vainio, Panu Oksa, Päivi Piirilä, Ari Hirvonen, Simo Kaleva, Tapio Vehmas, Mari K Kukkonen, Matti S. Huuskonen |
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| Rok vydání: | 2010 |
| Předmět: |
Lung Diseases
Male Quality Control Pulmonary and Respiratory Medicine medicine.medical_specialty Pathology Genotype Pulmonary Fibrosis EPHX1 medicine.disease_cause Gastroenterology Asbestos Xenobiotics Risk Factors Fibrosis Occupational Exposure Internal medicine Diffusing capacity medicine Genetic predisposition Humans Genetic Predisposition to Disease Lung volumes Lung Aged Glutathione Transferase Polymorphism Genetic business.industry Middle Aged medicine.disease medicine.anatomical_structure Female business Gene Deletion |
| Zdroj: | University of Helsinki |
| ISSN: | 1399-3003 0903-1936 |
| DOI: | 10.1183/09031936.00049810 |
| Popis: | The objective of this study was to determine whether genetic polymorphisms in enzymes that metabolise oxidative agents modify the individual susceptibility to developing asbestos and smoking-related pleuropulmonary changes. Nine polymorphisms of six genes (EPHX1, GSTM1, GSTM3, GSTP1, GSTT1 and NAT2) were genotyped from 1,008 Finnish asbestos-exposed workers. The genotype data were compared to signs of lung fibrosis and pleural thickenings, as well as with total lung capacity, single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) and specific diffusing capacity (expressed as D(L,CO) per unit of alveolar volume (V(A))). The GSTT1 deletion polymorphism was associated with fibrotic changes (p=0.003), and decreased D(L,CO) (p=0.02) and D(L,CO)/V(A) (p=0.002), and the GSTM1 deletion polymorphism was associated with the greatest thickness of pleural plaques (p=0.009). On further analysis, the GSTT1 null genotype was found to pose over a three-fold risk for severe fibrotic changes (OR 3.12, 95% CI 1.51-6.43), and around two-fold risks for decreased D(L,CO) (OR 1.77, 95% CI 1.06-2.95) and D(L,CO)/V(A) (OR 2.37, 95% CI 1.33-4.23). In addition, the GSTM1 null genotype showed an elevated risk (OR 1.36, 95% CI 1.03-1.80) for thicker pleural plaques. Our data suggest that inherited detoxification capacity may affect the development and severity of asbestos and smoking-related nonmalignant pulmonary changes. |
| Databáze: | OpenAIRE |
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