TNFA-863 polymorphism is associated with a reduced risk of chronic obstructive pulmonary disease: a replication study

• Published in: BMC genetics Vol. 12; no. 1; p. 132
• Main Authors: Córdoba-Lanús, Elizabeth, Baz-Dávila, Rebeca, de-Torres, Juan P, Rodríguez-Pérez, María C, Maca-Meyer, Nicole, Varo, Nerea, Medina-Coello, Chaxiraxi, Aguirre-Jaime, Armando, Casanova, Ciro
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10-10-2011; BioMed Central; BMC
• Subjects: Aged; Airway management; Body mass index; Care and treatment; Cohort Studies; Confidence intervals; Development and progression; Diagnosis; Drug therapy; Female; Genes; Genetic aspects; Genetic Predisposition to Disease; Haplotypes; Health aspects; Humans; Lung diseases, Obstructive; Male; Middle Aged; Physiological aspects; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - genetics; Risk Factors; Smokers; Tumor necrosis factor; Tumor Necrosis Factor-alpha - genetics; Spain
• ISSN: 1471-2350; 1471-2156; 1471-2350; 1471-2156
• DOI: 10.1186/1471-2350-12-132

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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.
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.
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 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).
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.