Genetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease

Tumour necrosis factor alpha (TNF-) has an important role in inflammatory response. Alterations in the regulation of TNF- have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF- inhibitors. Polymorphisms in the TNF- promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF- promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF- treatment. DNA samples from patients with IBD and controls were screened for TNF- -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF- inhibitors. There were not statistical differences in -238G/A and -308G/A allele and genotype frequencies between patients. However, we found an increased frequency of -308A allele and -308GA genotype in these nonresponders patients to TNF- inhibitors with respect to responders patients (Pc<0.05). This -308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF- inhibitors. TNF- promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF- genotypes may be involved in the different responses to TNF- inhibitor treatment in Spanish patients with IBD.