High-Throughput Whole-Exome Sequencing and Large-Scale Computational Analysis to Identify the Genetic Biomarkers to Predict the Vedolizumab Response Status in Inflammatory Bowel Disease Patients from Saudi Arabia.
PMID 40002872 | PMCID PMC11852680 | DOI 10.3390/biomedicines13020459 · Biomedicines · 2025 · View on PubMed ↗
Background/Objectives: Vedolizumab (VDZ) is the new monoclonal drug targeting α4β7 integrin for patients with moderate/severe IBD. Between 30 and 45% of patients fail to respond to VDZ after 14-16 weeks of treatment. The aim of the study was to explore the genetic profile of vedolizumab-treated Arab IBD patients in Saudi Arabia to identify the potential biomarkers to differentiate the responders from non-responders. Methods: A cohort of 16 patients with IBD, including 4 with Crohn's disease and 12 with ulcerative colitis, were recruited. Following 16 weeks of VDZ treatment, nine were found to be responders and seven non-responders. Blood samples were collected for the whole exome sequencing of DNA from all patients. The variants in the whole-exome sequencing data were analyzed with a variety of bioinformatics tools and databases, such as Polyphen2, Mutation Taster, CADD, FATHMM, Open Target Platform, TOPPFun, STRING, and GTEx. Results: More than 1.6 million variants from 16 samples were analyzed. The rare variant analysis prioritized NOD2, IL23, IL10, IL27, and TRAF1 genes in non-responders. NOD2, IL23, IL10, IL27, and TRAF1 were found to be the significant IBD risk factors in multiple genome-wide association studies, and their pro-inflammatory activity might contribute to the inherent resistance to VDZ. Rare variants of CARD9, TYK2, IL4, and NLRP1 genes present in VDZ responders enhance the anti-inflammatory/immune modulation effects. Conclusions: This investigation is the first to apply whole-exome sequencing to identify the potential drug response biomarkers for the IBD drug VDZ in Saudi Arabia.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | NOD2 | “The rare variant analysis prioritized NOD2, IL23, IL10, IL27, and TRAF1 genes in non-responders.” | 0.98 | hgnc_dict_v1 |
| gene | IL10 | “The rare variant analysis prioritized NOD2, IL23, IL10, IL27, and TRAF1 genes in non-responders.” | 0.98 | hgnc_dict_v1 |
| gene | IL27 | “The rare variant analysis prioritized NOD2, IL23, IL10, IL27, and TRAF1 genes in non-responders.” | 0.98 | hgnc_dict_v1 |
| gene | TRAF1 | “The rare variant analysis prioritized NOD2, IL23, IL10, IL27, and TRAF1 genes in non-responders.” | 0.98 | hgnc_dict_v1 |
| gene | CARD9 | “Rare variants of CARD9, TYK2, IL4, and NLRP1 genes present in VDZ responders enhance the anti-inflammatory/immune modulation effects.” | 0.98 | hgnc_dict_v1 |
| gene | TYK2 | “Rare variants of CARD9, TYK2, IL4, and NLRP1 genes present in VDZ responders enhance the anti-inflammatory/immune modulation effects.” | 0.98 | hgnc_dict_v1 |
| gene | IL4 | “Rare variants of CARD9, TYK2, IL4, and NLRP1 genes present in VDZ responders enhance the anti-inflammatory/immune modulation effects.” | 0.98 | hgnc_dict_v1 |
| gene | NLRP1 | “Rare variants of CARD9, TYK2, IL4, and NLRP1 genes present in VDZ responders enhance the anti-inflammatory/immune modulation effects.” | 0.98 | hgnc_dict_v1 |
| phenotype | inflammatory bowel disease | “High-Throughput Whole-Exome Sequencing and Large-Scale Computational Analysis to Identify the Genetic Biomarkers to Predict the Vedolizumab Response Status in Inflammatory Bowel Disease Patients from Saudi Arabia.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | ulcerative colitis | “Methods: A cohort of 16 patients with IBD, including 4 with Crohn's disease and 12 with ulcerative colitis, were recruited.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | Crohn disease | “Methods: A cohort of 16 patients with IBD, including 4 with Crohn's disease and 12 with ulcerative colitis, were recruited.” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “High-Throughput Whole-Exome Sequencing and Large-Scale Computational Analysis to Identify the Genetic Biomarkers to Predict the Vedolizumab Response Status in Inflammatory Bowel Disease Patients from Saudi Arabia. The aim of the study was to explore the genetic profile of vedolizumab-treated Arab IBD patients in Saudi Arabia to identify the potential biomarkers to differentiate the responders from non-responders. Methods: A cohort of 16 patients with IBD, including 4 with Crohn's disease and 12 with ulcerative colitis, were recruited. Conclusions: This investigation is the first to apply whole-exome sequencing to identify the potential drug response biomarkers for the IBD drug VDZ in Saudi Arabia.” | 0.95 | saudi_context_rules_v1 |