Associations of TNF-Α -308 and -238 Polymorphisms with Inflammatory Bowel Disease: A Case-Control Study and Meta-Analysis of Published Data

Shirin Moosavi; Aaron Shanker; Maryam Sadr; Samaneh Soltani; Sepideh Shahkarami; Elham Farhadi; Nasser Ebrahimi Daryani; Behnoud Baradaran Noveiry; Farnaz Najmi Varzaneh; Mohammad Bashashati; Nima Rezaei

doi:10.18502/igj.v8i2.18003

Shirin Moosavi Snyder Institute for Chronic Diseases, University of Calgary, 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
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
Farnaz Najmi Varzaneh Department of Radiology, Yale University, 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

DOI: https://doi.org/10.18502/igj.v8i2.18003

Keywords: Inflammatory Bowel Disease; Ulcerative Colitis; Crohn's Disease; Allele Frequency; Polymor- phisms; Meta-Analysis

Abstract

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 differ- ent populations.

Methods: Allele frequency and genotype status of TNF-α -308 and -238 SNPs were investigated in 75 un- related 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. TNF-α -308 AA gen- otype is positively correlated with UC in this meta-analysis.