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

Abstract

BackgroundTNF-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.MethodsThe 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.ResultsThe 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 FEV1 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).ConclusionsWe 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 promoter alleles – frequencies and linkage with classical HLA genes in a South German Caucasian population

“…The second most frequent SNP observed in our population was rs1800630 (−863). The A‐allele of this SNP has been associated with reduced circulating TNF levels and reduced risk in chronic obstructive pulmonary disease (COPD) by influencing affinity of nuclear transcription‐related proteins (NF‐κB) .…”

IL-8Gene Variants are Associated with Lung Function Decline and Multidimensional BODE Index in COPD Patients But Not with Disease Susceptibility: A Validation Study

“…COPD is thought to result from an abnormal pulmonary inflammatory response to noxious particles or gases (1) in which CD8+ Tc1 lymphocytes together with macrophages and neutrophils are supposed to play an important role (2)(3)(4). Many different inflammatory markers appear to be increased in the serum of stable COPD patients, or were associated with COPD risk, and worse outcomes of the disease (5)(6)(7)(8)(9).…”

Avaliação de polimorfismo de nucleotídeo único em gene promotor da citocina inflamatória IL6 quanto à susceptibilidade em doenças pulmonares

“…Muitos estudos sugerem que polimorfismos de nucleotídeo único (SNPs) em genes que codificam citocinas teriam relação à susceptibilidade a estas doenças pulmonares (COLAKOGULLARI et al, 2008;CÓRDOBA-LANÚS et al, 2011). Estes polimorfismos estariam influenciando a transcrição do gene, conduzindo a variações na produção de citocinas (HU et al, 2015).…”