Pro‐ and anti‐inflammatory cytokine gene single‐nucleotide polymorphisms in inflammatory bowel disease

Abstract

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: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFβ [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1β [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFβ, IL10, IL6, IL1α, IL1β, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C 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/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFβ, IL10, IL6 and IL1α, IL1β, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development.

Interleukin (IL)-1 Gene Cluster in Inflammatory Bowel Disease: Is IL-1RA Implicated in the Disease Onset and Outcome?

“…Although these results could enhance the understanding of the development and the clinical behavior of patients, other recent and similar studies have not reported any relationship between IL-1 gene cluster polymorphisms and IBD in populations of different ethnic origin [5,6,9].…”

“…Other members of IL-1 family have also been implicated in epithelial regeneration and mucosal wound healing (such as IL-33), in bowel inflammation and homeostasis (such as IL-36), and for potent anti-inflammatory activity (such as IL-37) with the ability to downregulate colitis. Polymorphisms of these genes are implicated in intestinal pathology [3][4][5][6].…”

Tumour necrosis factor‐alpha (‐308G/A) promoter polymorphism is associated with ulcerative colitis in Brazilian patients

“…Previous studies were able to find association between CD susceptibility and the IL‐10 promoter polymorphism in Mexican (Garza‐González et al ., ), New Zealand (Wang et al ., ) and United Kingdom (Tagore et al ., ) population. On the other hand, no association was found between the IL‐10 ‐1082 G/A polymorphism with CD or UC in Caucasians of United Kingdom (Koss et al ., ), Korean (Kim et al ., ), Canadian (Sanchez et al ., ), German (Klein et al ., ), Danish (Perrey et al ., and Andersen et al ., ) and Spanish population (Vatay et al ., ; Mendonza et al ., ; López‐Hernández et al ., ).…”

“…However, other studies in Australian (Fowler et al ., ), Canadian (Zipperlen et al ., ), Korean (Yang et al ., ), Caucasians (Koss et al ., ), Spanish (González et al ., ; López‐Hernández et al ., ) and Iranian (Nosratollah et al ., ) population found that rs1800629 promoter polymorphism was not associated with risk of Crohn's disease. In this sense, our results are in agreement with these data because the association between CD and controls was not statistically significant.…”

Interleukin-1 single nucleotide polymorphisms as risk factors for susceptibility of inflammatory bowel disease: an Iraqi Arab population-based study

“…Several SNPs have been described for IL1 genes and among these are IL1A −889 , IL1B −511 , IL1R1 pst1 1970 and IL1RA mspa1 11100 SNPs. Studies in CD and UC patients of different ethnicities have reported different correlations with the two forms of IBD, but some of them suggested that these polymorphisms may play a role in etiopathogenesis of IBD [12][13][14][15][16][17][18][19][20].…”