Unraveling genetic signatures: the impact of SNPs on therapy response in inflammatory bowel disease patients.

Authors

Nesa Kazemifard, Masomeh Askari, Leila Navapour, Anahita Tajik, Mina Faraji, Arvand Akbari, Navid Mogharrab, Shaghayegh Baradaran Ghavami, Hamid Asadzadeh Aghdaei

Published in

Gastroenterology and hepatology from bed to bench. Volume 18. Issue SI. Pages 97-109. Epub Dec 29, 2025.

Abstract

Inflammatory bowel disease (IBD) is a chronic condition characterized by immune dysregulation and intestinal inflammation, with anti-tumor necrosis factor α (anti-TNFα) therapies being a key treatment strategy. However, therapeutic responses vary across patients due to genetic factors, necessitating the identification of predictive biomarkers to optimize outcomes. This study employs bioinformatic approaches to investigate the deleterious effects of SNPs in IBD-associated genes, focusing on the structural implications of HFE gene variants and the impact of TNFRSF1B 3' UTR SNPs on miRNA binding site alterations.
The study utilized a systematic literature review to identify genes influencing drug response in IBD, followed by SNP detection. SNPs were filtered based on population frequencies using global databases (gnomAD, ExAC) and Iranome for region-specific data. Structural and functional impacts of missense variants were evaluated using in silico tools and protein domain analysis via InterPro and UniProt. Additionally, molecular dynamics simulation indicated structural changes in HFE gene variants, RNA-seq data analyzed differential gene expression, and miRNASNP-v3 predicted miRNA binding site alterations in 3' UTR regions.
A comprehensive bioinformatics approach identified 41 key IBD drug response genes contributing to cellular pathways, with 69 coding sequence SNPs and 27 3'-UTR SNPs selected for analysis. Coding SNPs, including ABCB1 and HFE variants, were predicted to significantly alter protein structure and stability. RNA-seq analysis revealed TNFRSF1B upregulation in IBD patients, and its 3'-UTR SNPs were shown to affect miRNA binding. Molecular dynamics simulation demonstrated structural instability in the HFE H63D variant, suggesting functional disruption.
This study explores genetic variations influencing anti-TNF therapy responses in IBD patients. Polymorphisms like HFE rs1799945 and TNFRSF1B SNPs are identified as pivotal markers for personalized treatment strategies. Computational findings highlight their clinical potential, emphasizing the need for experimental validation to advance precision medicine and improve therapeutic outcomes and quality of life in IBD management.

PMID:
42137132
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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