Associations of inflammatory cytokines with inflammatory bowel disease: a Mendelian randomization study

Abstract

ObjectivesPrevious studies have confirmed a link between specific inflammatory cytokines and inflammatory bowel disease (IBD), but the causal relationship between them is not completely clear. This Mendelian Randomization (MR) study aims to evaluate the causal relationship between 18 inflammatory cytokines and inflammatory bowel disease.MethodTwo-sample Mendelian randomization utilized genetic variances associated with IBD from two extensive publicly available genome-wide association studies (GWAS) (Crohn’s Disease (CD): 12,194 cases and 28,072 controls; Ulcerative Colitis (UC): 12,336 cases and 33,609 controls). The data of inflammatory cytokines was acquired from a GWAS including 8,293 healthy participants. We used inverse variance weighted method, MR-Egger, weighted median, simple model and weighted model to evaluate the causal relationship between inflammatory cytokines and IBD. Sensitivity analysis includes heterogeneity and pleiotropy analysis to evaluate the robustness of the results.ResultsThe findings indicated suggestive positive associations between Interleukin-13 (IL-13) and macrophage migration inhibitory factor (MIF) with CD (odds ratio, OR: 1.101, 95%CI: 1.021-1.188, p = 0.013; OR: 1.134, 95%CI: 1.024-1.255, p = 0.015). IL-13 also displayed a significant positive correlation with UC (OR: 1.099, 95%CI: 1.018-1.186, p = 0.016). Stem cell factor (SCF) was suggested to be associated with the development of both CD and UC (OR: 1.032, 95%CI: 0.973-1.058, p = 0.012; OR: 1.038, 95%CI: 1.005-1.072, p = 0.024).ConclusionThis study proposes that IL-13 may be a factor correlated with the etiology of IBD (CD and UC), while MIF just be specifically associated with CD. Additionally, SCF appears more likely to be involved in the downstream development of IBD (CD and UC).

Glycyrol Relieves Ulcerative Colitis by Promoting the Fusion of ZO-1 with the Cell Membrane through the Enteric Glial Cells GDNF/RET Pathway

“…Damage to the mechanical barrier of the intestinal mucosa is a prerequisite for triggering abnormal intestinal immunity, inflammation, and ulcer formation. It is the initiating factor and core link in the progression of UC, as well as a key target for alleviating UC. − Tight junction protein ZO-1 is a key scaffold protein for the intestinal mucosal mechanical barrier. In this study, we found that compared to the damaged mechanical barrier, the expression level of ZO-1 protein was increased in the intact mechanical barrier and its fusion level with the cell membrane was also significantly increased.…”

Genetically predicted associations between circulating cytokines and autoimmune diseases: a bidirectional two-sample Mendelian randomization

“…Initially, cytokine-related SNPs were selected, with the significance threshold set to P < 5 × 10 –8 to avoid biases from false-positive genetic tools. For exposures with few identified SNPs, the threshold for selecting cytokine genetic tools was raised to P < 5 × 10 –6 ( 19 ). Important SNP data were then extracted.…”

Associations of inflammatory cytokines with palmoplantar pustulosis: a bidirectional Mendelian randomization study

“…In the initial stages, we used a p-value of <5 × 10 −8 as the genomewide significance level to identify significantly associated SNPs connected to inflammatory cytokines and PPP. However, a higher cutoff (p < 5 × 10 −6 ) was used because there were only a few SNPs for several inflammatory cytokines when considered as exposure (30,31).…”