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. © The Japan Society of Human Genetics and Springer-Verlag 2006.

Item Type:	Refereed Article
Research Division:	Medical and Health Sciences
Research Group:	Cardiorespiratory Medicine and Haematology
Research Field:	Respiratory Diseases
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Respiratory System and Diseases (incl. Asthma)
Author:	Walters, EH (Professor Haydn Walters)
ID Code:	38992
Year Published:	2006
Web of Science® Times Cited:	23
Deposited By:	Medicine (Discipline)
Deposited On:	2006-08-01
Last Modified:	2007-03-28
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