title: Genetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease.
abstract: Tumour necrosis factor alpha (TNF-α) has an important role in inflammatory response. Alterations in the regulation of TNF-α 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-α inhibitors. Polymorphisms in the TNF-α 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-α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF-α treatment. DNA samples from patients with IBD and controls were screened for TNF-α -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF-α 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-α 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-α inhibitors. TNF-α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF-α genotypes may be involved in the different responses to TNF-α inhibitor treatment in Spanish patients with IBD.
authors.affiliation: Immunology Service, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: R
authors.initials: R
authors.lastname: López-Hernández
authors.forename: M
authors.initials: M
authors.lastname: Valdés
authors.forename: J A
authors.initials: JA
authors.lastname: Campillo
authors.forename: P
authors.initials: P
authors.lastname: Martínez-Garcia
authors.forename: H
authors.initials: H
authors.lastname: Salama
authors.forename: G
authors.initials: G
authors.lastname: Salgado
authors.forename: F
authors.initials: F
authors.lastname: Boix
authors.forename: M R
authors.initials: MR
authors.lastname: Moya-Quiles
authors.forename: A
authors.initials: A
authors.lastname: Minguela
authors.forename: A
authors.initials: A
authors.lastname: Sánchez-Torres
authors.forename: M
authors.initials: M
authors.lastname: Miras
authors.forename: A
authors.initials: A
authors.lastname: Garcia
authors.forename: F
authors.initials: F
authors.lastname: Carballo
authors.forename: M R
authors.initials: MR
authors.lastname: Álvarez-López
authors.forename: M
authors.initials: M
authors.lastname: Muro
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013030:Spain; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha