Tumour necrosis factor gene polymorphisms are associated with chronic obstructive pulmonary disease

¹ Dept of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO
² Dept of Medicine, National Jewish Medical and Research Center, Denver, CO
³ Dept of Medicine, Denver Veterans Affairs Medical Center, Denver CO, University of Colorado Cancer Center
⁴ Dept of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO; Dept of Medicine, National Jewish Medical and Research Center, Denver, CO; and Dept of Medicine, Denver Veterans Affairs Medical Center, Denver CO, University of Colorado Cancer Center

^* To whom correspondence should be addressed. E-mail: BowlerR{at}njc.org.

	Abstract

tumour necrosis factor- (TNF-) has been shown to be an important factor in animal models of Chronic Obstructive Pulmonary Disease (COPD); however, human studies of TNF polymorphisms in COPD have been equivocal. We investigated six TNF single nucleotide polymorphisms (SNPs) (-1031C/T, -863C/A, -857C/T, -237G/A, -308G/A, +487G/A) and their haplotypes in 423 Caucasian smokers (298 with spirometric evidence of COPD patients and 125 without airflow obstruction). The -308 minor allele (A) was associated with a higher odds ratio (OR) of being associated with COPD in multivariate analysis (controlling for age, sex, pack-years; OR 1.9; 95%CI 1.1–3.2, p=0.03) and was also associated with worse FEV₁/FVC (p=0.03). The -237 minor allele (A) had a lower OR of being associated with COPD (OR 0.40; 95%CI 0.19–0.86, p=0.02). In COPD patients, the -857 minor allele (T) had a lower OR of being associated with severe stages of COPD (GOLD stage 3 and 4 versus stage 1 and 2; OR 0.46; 95%CI 0.24–0.88, p=0.02). Other TNF SNPs were not associated with COPD; however the -1031/-863 haplotype CC/TC had a lower OR in COPD patients versus smoking controls (OR 0.22; 95%CI 0.05–.97, p=0.05). This study adds further evidence that TNF genotypes play a role in susceptibility to cigarette smoke.