Texas Tech University Health Sciences Center El Paso, TX
Aaron Shanker, MD1, Alejandro Robles, MD1, Abhizith Deoker, MD1, Irene Sarosiek, MD1, Nasser Ebrahimi Daryani, MD2, Ali Rezaie, MD3, Nima Rezaei, MD4, Max Schmulson, MD5, Marc Zuckerman, MD1, Mohammad Bashashati, MD1; 1Texas Tech University Health Sciences Center, El Paso, TX; 2Tehran University of Medical Sciences, Tehran, Tehran, Iran; 3Cedars-Sinai, Los Angeles, CA; 4Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Tehran, Iran; 5Universidad Nacional Autónoma de México (UNAM), Hospital General de México, Mexico City, Distrito Federal, Mexico
Introduction: Cytokines are imbalanced in irritable bowel syndrome (IBS) and polymorphisms of cytokine-encoding genes may alter the risk of developing IBS. Whether IBS and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are separate entities or are on a spectrum with overlap is a question which has not been sufficiently explored. This study aimed to understand whether cytokine gene polymorphisms which are observed in IBS are also associated with IBD. Methods: We designed a network meta-analysis to compare the distribution of three cytokine gene polymorphisms that have been more frequently studied in IBS and IBD: IL-10 (-1082GA), IL6 (-174GC), and TNF-α (-308GA). PubMed and Embase were searched for studies on the distribution of these polymorphisms in IBS and IBD vs. control. NetMetaXL (CADTH, Ottawa, Canada) was used for conducting this Bayesian network meta-analysis. Vague prior < 0.5 suggested lower heterogeneity where fixed effects model was used. Odds ratio (OR) with 95% credible intervals [95% Cr.I.]. was used for the comparisons. Results: Ten studies on IBS vs. controls, one on IBS vs. IBD vs. controls, and thirty-nine comparing IBD vs. controls, were included. The high producer IL-10 (-1082GG) genotype was less frequent in IBS vs. the three other groups: Controls 0.66 [0.50 – 0.88], UC 0.66 [0.47 – 0.91], and CD 0.72 [0.52 – 0.98]; while the intermediate producer IL-10 (-1082GA) was more frequently observed in IBS vs. Controls and UC. When comparing the low producer IL-10 (-1082AA) genotype in IBS with either IBD groups or Controls, no significant difference was observed, while CD had a lower frequency of IL-10 (-1082AA) vs. Controls. The high producer TNF-α (-308AA) was similarly distributed in IBS vs. other groups and was less frequent in Controls vs. UC: 0.68 [0.46 – 0.99]. TNF-α (-308 GG and GA) was similar among the study groups. IL6 (-174GC) was less frequent in IBS vs. CD: 0.73 [0.55 – 0.98]; and in UC vs. CD: 0.69 [0.53 – 0.89]. The high producer IL6 (-174GG) was less frequent in CD vs. UC: 0.73 [0.56-0.95]; while no difference was observed in IBS vs. other groups. Discussion: IL-10 (-1082GA) has a more prominent role than TNF-α (-308GA) and IL6 (-174GC) in the pathogenesis of IBS and may distinguish IBS from IBD. There is a shift toward high producer pro-inflammatory TNF-α (-308AA) and IL6 (-174GG) in UC, distinguishing it from the other groups.
Disclosures: Aaron Shanker indicated no relevant financial relationships. Alejandro Robles indicated no relevant financial relationships. Abhizith Deoker indicated no relevant financial relationships. Irene Sarosiek indicated no relevant financial relationships. Nasser Ebrahimi Daryani indicated no relevant financial relationships. Ali Rezaie indicated no relevant financial relationships. Nima Rezaei indicated no relevant financial relationships. Max Schmulson indicated no relevant financial relationships. Marc Zuckerman indicated no relevant financial relationships. Mohammad Bashashati indicated no relevant financial relationships.