Related Experiment Video
Updated: Nov 12, 2025
Investigating Target Gene Function in a CD40 Agonistic Antibody-induced Colitis Model using CRISPR/Cas9-based Technologies
Published on: June 2, 2021
NGS study of glucocorticoid response genes in inflammatory bowel disease patients
Marzena Skrzypczak-Zielinska1, Marcin Gabryel2, Daria Marszalek1
1Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Introduction:
Despite intensive research and a long history of glucocorticoids being applied in various clinical areas, they still generate a challenge for personalized medicine by causing resistance or dependence in nearly 50% of patients treated. The objective of the present study was to determine the genetic predictors of variable reactions in inflammatory bowel disease patients to glucocorticoid therapy. Therefore, based on the current knowledge on how glucocorticoids act, we have compiled a panel of 21 genes for variant analysis: NR3C1, NLRP1, IPO13, FKBP5, HSPA4, ABCB1, STIP1, HSP90AA1, IL-1A, IL-1B, IL-2, IL-4, CXCL8, IL-10, NFKBIA, JUN, MIF, TNF, MAPK14, CYP3A4, and CYP3A5.
Material And Methods:
These genes were analyzed using the amplicon next-generation sequencing method in a group of 139 diagnosed and clinically characterized inflammatory bowel disease patients with a confirmed glucocorticoid response.
Results:
Analysis of all the targeted DNA sequences for the whole patient group indicated 121 different functional variants. After association analyses of 31 selected variants, the polymorphism c.1088A>G in the NR3C1 gene was linked with glucocorticoid resistance (p = 0.002), variant c.241+6A>G of the FKBP5 gene with glucocorticoid sensitivity (p = 0.040), and deletion c.306-7delT in the MAPK14 gene with an adverse therapeutic effect (dependency and resistance, p = 0.041) in ulcerative colitis patients. In Crohn's disease, the change c.2685+49T>C of the ABCB1 gene related to glucocorticoid resistance (p = 0.034).
Conclusions:
Among the 21 analyzed genes, four (NR3C1, FKBP5, MAPK14, and ABCB1) revealed a significant impact on the glucocorticoid treatment response, which could result in valuable pharmacogenetic biomarkers after being confirmed in other populations and in functional studies.
Insights
Genetic variants in four genes, including NR3C1 and FKBP5, predict patient response to glucocorticoids, offering potential for personalized inflammatory bowel disease treatment. These findings may lead to new pharmacogenetic biomarkers.
Area of Science:
- Pharmacogenomics
- Molecular biology
- Gastroenterology
Background:
- Glucocorticoids are widely used but show variable efficacy and side effects in nearly 50% of patients.
- Personalized medicine approaches are needed to optimize glucocorticoid therapy.
- Identifying genetic predictors of response is crucial for tailoring treatment.
Purpose of the Study:
- To identify genetic predictors of variable responses to glucocorticoid therapy in inflammatory bowel disease (IBD) patients.
- To analyze genetic variants in a panel of 21 genes involved in glucocorticoid action.
Main Methods:
- Amplicon next-generation sequencing was used to analyze 21 candidate genes in 139 IBD patients.
- Patients had confirmed clinical characterization and glucocorticoid response.
- Association analyses were performed on selected genetic variants.
Main Results:
- 121 functional variants were identified across the 21 genes.
- Specific polymorphisms in NR3C1, FKBP5, MAPK14, and ABCB1 genes were significantly associated with glucocorticoid resistance, sensitivity, or adverse effects.
- NR3C1 (c.1088A>G) linked to resistance; FKBP5 (c.241+6A>G) linked to sensitivity; MAPK14 (c.306-7delT) linked to adverse effects in ulcerative colitis; ABCB1 (c.2685+49T>C) linked to resistance in Crohn's disease.
Conclusions:
- Four genes (NR3C1, FKBP5, MAPK14, ABCB1) showed significant associations with glucocorticoid treatment response in IBD.
- These genetic variants represent potential pharmacogenetic biomarkers for personalized glucocorticoid therapy.
- Further validation in diverse populations and functional studies are recommended.
More Related Videos
09:31Effects of Taste Signaling Protein Abolishment on Gut Inflammation in an Inflammatory Bowel Disease Mouse Model
Published on: November 9, 2018
10:21Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
Related Concept Videos
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...