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Background  TNF-α mediated inflammation is thought to play a key role in the respiratory and systemic features of Chronic Obstructive Pulmonary Disease. The aim of the present study was to replicate and extend recent findings in Taiwanese and Caucasian populations of associations between COPD susceptibility and variants of the  TNFA  gene in a Spanish cohort.    Methods  The 3 reported SNPs were complemented with nine tag single nucleotide polymorphisms (SNP) of the  TNFA  and  LTA  genes and genotyped in 724 individuals (202 COPD patients, 90 smokers without COPD and 432 healthy controls). Pulmonary function parameters and serum inflammatory markers were also measured in COPD patients.    Results  The  TNFA  rs1800630 (-863C/A) SNP was associated with a lower COPD susceptibility (ORadj = 0.50, 95% CI = 0.33-0.77, p = 0.001). The -863A allele was also associated with less severe forms of the disease (GOLD stages I and II) (ORadj = 0.303, 95%CI = 0.14-0.65, p = 0.014) and with lower scores of the BODE index (< 2) (ORadj = 0.40, 95%CI = 0.17-0.94, p = 0.037). Moreover, the -863A carrier genotype was associated with a better FEV 1  percent predicted (p = 0.004) and a lower BODE index (p = 0.003) over a 2 yrs follow-up period. None of the  TNFA  or  LTA  gene variants correlated with the serum inflammatory markers in COPD patients (p > 0.05).    Conclusions  We replicated the previously reported association between the  TNFA  -863 SNP and COPD.  TNFA  -863A allele may confer a protective effect to the susceptibility to the disease in the Spanish population.

TNFA-863 polymorphism is associated with a reduced risk of Chronic Obstructive Pulmonary Disease: A replication study