ArticlePloS one2010
Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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Who cites it
46 citing papers in PubMed, 125 citations in OpenAlex.
- Gut-Liver Axis, Microbiota, Bile Acids, and Immune Response in Pathogenesis of Primary Sclerosing Cholangitis: An Overview.Journal of clinical medicine · 2025Review
- Structure-Based Insights into TGR5 Activation by Natural Compounds: Therapeutic Implications and Emerging Strategies for Obesity Management.Biomedicines · 2025Review
- Bile acid metabolism in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Bile acids and their receptors in hepatic immunity.Liver research (Beijing, China) · 2025Review
- Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments.Cells · 2024Review
- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
- Research Progress of Takeda G Protein-Coupled Receptor 5 in Metabolic Syndrome.Molecules (Basel, Switzerland) · 2023Review
- Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD): a condition exemplifying the crosstalk of the gut-liver axis.Experimental & molecular medicine · 2023Review
- Role of Takeda G protein‑coupled receptor 5 in microvascular endothelial cell dysfunction in diabetic retinopathy (Review).Experimental and therapeutic medicine · 2022Review
- Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.Seminars in immunopathology · 2022Review
- Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: A Review.Journal of clinical and translational hepatology · 2022Review
- Review
- Modulation of Bile Acid Metabolism to Improve Plasma Lipid and Lipoprotein Profiles.Journal of clinical medicine · 2021Review
- Bile Acid Signaling in Inflammatory Bowel Disease.International journal of molecular sciences · 2021Review
- Bile Acid Signaling in Inflammatory Bowel Diseases.Digestive diseases and sciences · 2021Review
- Intrahepatic macrophage populations in the pathophysiology of primary sclerosing cholangitis.JHEP reports : innovation in hepatology · 2019Article
- Preclinical insights into cholangiopathies: disease modeling and emerging therapeutic targets.Expert opinion on therapeutic targets · 2019Review
- Mechanisms of cholangiocyte responses to injury.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease.Frontiers in endocrinology · 2018Review
- Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
37 authors at 14 institutions in 6 countries.
Funding
Abstract
backgroundTGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC, as well as functionally characterize detected variants. METHODOLOGY/PRINCIPAL
findingsComplete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor model, and introduced mutated TGR5 constructs into human epithelial cell lines. By using confocal microscopy, flow cytometry and a cAMP-sensitive luciferase assay, five of the nonsynonymous mutations (W83R, V178M, A217P, S272G and Q296X) were found to reduce or abolish TGR5 function. Fine-mapping of the previously reported PSC and UC associated locus at chromosome 2q35 in large patient panels revealed an overall association between the TGR5 single-nucleotide polymorphism rs11554825 and PSC (odds ratio = 1.14, 95% confidence interval: 1.03-1.26, p = 0.010) and UC (odds ratio = 1.19, 95% confidence interval 1.11-1.27, p = 8.5 x 10(-7)), but strong linkage disequilibrium precluded demarcation of TGR5 from neighboring genes. CONCLUSIONS/SIGNIFICANCE: Resequencing of TGR5 along with functional investigations of novel variants provided unique insight into an important candidate gene for several inflammatory and metabolic conditions. While significant TGR5 associations were detected in both UC and PSC, further studies are needed to conclusively define the role of TGR5 variation in these diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.