ArticleGastroenterology2011
A Klothoβ variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Pooled it
- Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023.Digestion · 2024Guideline
- A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome.The Journal of clinical investigation · 2020Trial
- Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea.Digestive diseases and sciences · 2012Trial
- Review
- Unraveling the Pathophysiology of Irritable Bowel Syndrome: Mechanisms and Insights.International journal of molecular sciences · 2025Review
- Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism.Expert opinion on drug metabolism & toxicology · 2024Review
- Association of the rs1966265 and rs351855Biomedicines · 2024Article
- Targeting the FGF19-FGFR4 pathway for cholestatic, metabolic, and cancerous diseases.Journal of internal medicine · 2024Review
- Farnesoid X Receptor Agonist GW4064 Protects Lipopolysaccharide-Induced Intestinal Epithelial Barrier Function and Colorectal Tumorigenesis Signaling through the αKlotho/βKlotho/FGFs Pathways in Mice.International journal of molecular sciences · 2023Article
- Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho.Frontiers in endocrinology · 2023Review
- Genetics of irritable bowel syndrome: shifting gear via biobank-scale studies.Nature reviews. Gastroenterology & hepatology · 2022Review
- Pathophysiology and Clinical Management of Bile Acid Diarrhea.Journal of clinical medicine · 2022Review
- A Recent Ten-Year Perspective: Bile Acid Metabolism and Signaling.Molecules (Basel, Switzerland) · 2022Review
- GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome.Cell genomics · 2021Article
- SLC10A2 deficiency-induced congenital chronic bile acid diarrhea and stunting.Molecular genetics & genomic medicine · 2021Article
- Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer.Diagnostics (Basel, Switzerland) · 2021Article
- Bile pigment in small-bowel water content may reflect bowel habits: a retrospective analysis of a capsule endoscopy imaging series.BMC gastroenterology · 2020Article
- Bile Acid Diarrhea and NAFLD: Shared Pathways for Distinct Phenotypes.Hepatology communications · 2020Review
- Irritable Bowel Syndrome between Molecular Approach and Clinical Expertise-Searching for Gap Fillers in the Oxidative Stress Way of Thinking.Medicina (Kaunas, Lithuania) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsBile acid (BA) malabsorption of moderate severity is reported in 32% of patients with chronic unexplained diarrhea, including diarrhea-predominant irritable bowel syndrome (IBS-D). We hypothesized that variants of genes regulating hepatic BA synthesis play a role in IBS-D.
methodsIn 435 IBS and 279 healthy subjects, we tested individual associations of 15 common single nucleotide polymorphisms (SNPs) from 7 genes critical to BA homeostasis with symptom-based subgroups using dominant genetic models. In a subset of 238 participants, we tested association with colonic transit. SNP-SNP interactions were investigated based on known protein interactions in BA homeostasis. The function of SNP rs17618244 in Klothoβ (KLB) was evaluated using a protein stability assay in HEK293 cells.
resultsSNP rs17618244 (Arg728Gln in KLB) is associated with colonic transit at 24 hours. G allele (Arg728) compared with A allele (Gln728) is associated with accelerated colonic transit (P=.0007) in the overall cohort; this association was restricted to IBS-D (P=.0018). Interaction tests of KLB rs17618244 with 3 nonsynonymous SNPs of fibroblast growth factor receptor 4 (FGFR4) revealed that rs1966265 (Val10Ile) and rs351855 (Gly388Arg) modulate rs1768244's association with colonic transit in IBS-D (P=.0025 and P=.0023, respectively). KLB Arg728 significantly reduced protein stability compared with KLB Gln728, demonstrating KLB rs17618244's functional significance. No significant associations with symptom-based subgroups of IBS were detected.
conclusionsA functional KLB gene variant mediating protein stability associates with colonic transit in IBS-D. This association is modulated by 2 genetic variants in FGFR4. The FGF19-FGFR4-KLB pathway links regulation of BA synthesis to colonic transit in IBS-D.
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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.