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, British Columbia, Canada
² Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
³ Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

^* To whom correspondence should be addressed. E-mail: asandford{at}mrl.ubc.ca.

	Abstract

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

We 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 year follow up period, and the second included the subjects who had the lowest (n=533) and the highest (n=532) post bronchodilator FEV₁% predicted at the start of the LHS. We selected and genotyped 10 tagging SNPs within the TNF and LTA region.

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

These results support the findings of previous studies in late-onset COPD in Caucasian populations.

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