Abstract
Chronic obstructive pulmonary disease (COPD) is a disease characterised by inflammation of the peripheral airways involving many inflammatory cells and mediators. IL8 is an important inflammatory mediator that is responsible for the migration and activation of neutrophils. Cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by the cytokine tumour necrosis factor (TNFα). The aim of our study was to investigate the influence of single nucleotide polymorphisms in IL8, CXCR2 and TNF-α on lung function and respiratory symptoms in subjects from Melbourne, Australia. A total of 1,232 participants completed a detailed respiratory questionnaire, spirometry and measurement of gas transfer. Genotyping for the IL8 -251 T→A, CXCR2 +785C→T and TNF-α -308G→A polymorphisms was performed using the tetra-primer ARMS-PCR method. The TNF-α A allele was associated with a reduced FEF25–75 (P=0.03). Inheritance of the CXCR2 T allele was associated with significantly higher diffusing capacity (P=0.03) and FEF25–75 (P=0.02). No association with the IL8 -251 polymorphism was found. Our results suggest that TNF-α is associated with COPD-related phenotypes and the CXCR2 +785 SNP may be important in protecting against pulmonary inflammation. These genes may be important candidates in the modulation of the inflammatory response in the airways.
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Acknowledgements
We acknowledge the financial support provided by The National Health & Medical Research Council of Australia, Monash University, LEW Carty Research Fund, Windermere Foundation, Victorian Tuberculosis & Lung Association and the Rebecca L Cooper Medical Research Foundation, to enable this study to be undertaken. We wish to thank Associate Professor David Johns for advice with regard to the lung function testing. We also acknowledge the assistance of Cathryn Wharton, Judi Wicking and Billy Skoric with data collection and Nicholas Harrap and Nadia Harun for assistance with DNA extraction.
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Matheson, M.C., Ellis, J.A., Raven, J. et al. Association of IL8, CXCR2 and TNF-α polymorphisms and airway disease. J Hum Genet 51, 196–203 (2006). https://doi.org/10.1007/s10038-005-0344-7
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DOI: https://doi.org/10.1007/s10038-005-0344-7
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