Tehran University of Medical Sciences Immunology and Genetics Journal 2645-4831 8 2 2025 03 04 236 247 Shirin Moosavi Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada; Microbiome and Microbial Ecology Interest Group (MMEIG), Universal Scientific Education and Research Network (USERN), Alberta, Canada Aaron Shanker Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA Maryam Sadr Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Samaneh Soltani Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Sepideh Shahkarami Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany; Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Munich, Germany Elham Farhadi Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Nasser Ebrahimi Daryani Division of Gastroenterology, Department of Medicine, Tehran University of Medical Sciences, Tehran, Iran Behnoud Baradaran Noveiry Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland, USA; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Baltimore, Maryland, USA Farnaz Najmi Varzaneh Department of Radiology, Yale University, New Haven, Connecticut, USA; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), New Haven, Connecticut, USA Mohammad Bashashati Division of Gastroenterology, Department of Medicine, Dell Medical School at UT Austin, Austin, TX, USA Nima Rezaei Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran 2025 03 04 2025 03 04 Background: Inflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory disease of the intestinal tract. Tumor necrosis factor-alpha (TNF-α) signaling plays a major role in the pathogenesis of IBD and is commonly targeted for therapeutic purposes. Results on the contribution of TNF-α -308 and -238 single nucleotide polymorphisms (SNP) to the susceptibility to IBD have been contradictory in different populations. Methods: Allele frequency and genotype status of TNF-α -308 and -238 SNPs were investigated in 75 unrelated patients with IBD [40 Crohn’s disease (CD) and 35 ulcerative colitis (UC)] and 140 healthy controls by polymerase chain reaction with sequence-specific primers (PCR-SSP). We also conducted a systematic review and meta-analysis of the published reports. Results: TNF-α -238 GG was detected at a higher frequency in CD and UC. TNF-α -308 GG was more frequently detected in UC compared to control. There was no significant association between TNF-α -238 or -308 gene polymorphisms and patients’ demography (i.e., gender and age) or disease phenotype (i.e., extraintestinal manifestations, treatment, activity index, age at onset, and duration of the disease). In the meta-analysis, TNF-α -238 (AA/AG) genotype tended to be less frequent in patients with UC compared to healthy controls. There was no association between TNF-α -238 gene polymorphisms (AA/AG or GG genotypes) and either form of IBD. Conclusion: TNF-α -308 and -238 SNPs are associated with IBD in Iranian patients. The TNF-α -308 AA genotype is positively correlated with UC in this meta-analysis. https://igj.tums.ac.ir/index.php/igj/article/view/202 https://igj.tums.ac.ir/index.php/igj/article/download/202/180