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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., (© 2013 John Wiley & Sons Ltd.)

MICA is located at 46 kb centromeric of HLA-B, is highly polymorphic and interactions with NKG2D, its receptor on the surface of NK, Tgammadelta, and T CD8 lymphocytes. A variation at amino acid position 129 of the alpha2-heavy chain domain seems to categorize MICA alleles into strong and weak binder of NKG2D receptor, and thereby to influence effector cell function. Our aim was to study allele polymorphism of MICA and the functionally relevant dimorphism (129val/met) of MICA gene in inflammatory bowel disease (IBD) patients in our population. DNA was obtained from IBD patients (n = 88) and unrelated healthy Murcians (n = 154) and used to MICA genotyping using polymerase chain reaction-sequence-specific oligonucleotides. We did not find statistical differences in the distribution of MICA alleles between the IBD and control groups. However, we found a higher frequency of MICA-129met/met and a lower frequency of MICA-129val/met genotypes in IBD patients (mainly in ulcerative colitis) than in controls (pc = 0.02). These preliminary data could suggest a relevant role of MICA-129-val/met SNP (weak/strong binders of NKG2D receptor) in the pathogenesis of IBD., (Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [ Crohn′s disease ( CD) and ulcerative colitis ( UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR- SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNF α [−238G/ A (rs361525) and −308 G/ A (rs1800629)], IFN γ [+874 A/ T (rs62559044)], TGF β [+869 C/ T (rs1982073) and +915 G/ C (rs1800471)], IL10 [−1082 A/ A (rs1800896), −592 A/ C (rs1800872), −819 C/ T (rs1800871)], IL6 [−174 C/ G (rs1800795)], IL12p40 [3′ UTR −1188 A/ C (rs3212227)], IL1 α [−889 C/ T (rs1800587)], IL1 β [−511 C/ T (rs1143634) and +3962 C/ T (rs1143633)], IL1 R [ Pst-1 1970 C/ T] and IL1 RA [ Mspa-1 11100 C/ T]. No statistical differences in TNF α, IFNγ, TGFβ, IL10, IL6, IL1α, IL1β, IL1 R and IL1 Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3′ UTR −1188 A/ C polymorphism of IL12p40. So −1188 A allele was increased in patients with UC and the −1188 C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/ IFN γ production at histological affected sites. These data suggest that cytokine polymorphisms in TNF α, IFNγ, TGFβ, IL10, IL6 and IL1α, IL1β, IL1 R and IL1 Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3′ UTR −1188 A/ C polymorphism seems to be associated with a differential IBD development. [ABSTRACT FROM AUTHOR]