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Tumour necrosis factor and lymphotoxin A polymorphisms and lung function in smokers

¹ James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, University of British Columbia, Vancouver, BC, and ³ Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada. ² Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

CORRESPONDENCE: A. J. Sandford, The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6 Canada. Fax: 1 6048068351. E-mail: asandford{at}mrl.ubc.ca

Keywords: Forced expiratory volume in one second, lymphotoxin A, polymorphism, smoking, tumour necrosis factor

Received: March 31, 2006
Accepted August 15, 2006

Genetic variants in the tumour necrosis factor (TNF) gene have been investigated in chronic obstructive pulmonary disease (COPD). However, there are many instances of nonreplication of these associations due to insufficient power or other factors. In this study, a large number of subjects were examined to elucidate whether genetic variations of TNF and/or lymphotoxin A (LTA), which is clustered with TNF, are associated with variations in lung function among smokers.

The present authors designed two nested case–control studies in the National Heart, Lung, and Blood Institute Lung Health Study (LHS), which enrolled 5,887 smokers. The first design included continuous smokers who had the fastest (n = 279) and the slowest (n = 304) decline of lung function during the 5-yr follow-up period, and the second included the subjects who had the lowest (n = 533) and the highest (n = 532) post-bronchodilator % predicted forced expiratory volume in one second at the start of the LHS. Within the TNF and LTA region, 10 tagging single-nucleotide polymorphisms were selected and genotyped.

Unlike the previous associations between TNF-308 and COPD in Asians, the current study found no association between either of the two phenotypes and the LTA and TNF polymorphisms.

In conclusion, these results support the findings of previous studies in late-onset chronic obstructive pulmonary disease in Caucasian populations.

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