ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Pooled it
- A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome.The Journal of clinical investigation · 2020Trial
- Enteric nervous system in microbiota-associated gut inflammation.Frontiers in immunology · 2026Review
- The Enteric Neuronal Circuitry: A Key Ignored Player in Nutrient Sensing Along the Gut-Brain Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism.Expert opinion on drug metabolism & toxicology · 2024Review
- [Bile Acid Diarrhea].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024Review
- Targeting the FGF19-FGFR4 pathway for cholestatic, metabolic, and cancerous diseases.Journal of internal medicine · 2024Review
- Pathophysiology and Clinical Management of Bile Acid Diarrhea.Journal of clinical medicine · 2022Review
- Bile Acid Diarrhea in Adults and Adolescents.Neurogastroenterology and motility · 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
- The Role of Bile Acids in Chronic Diarrhea.The American journal of gastroenterology · 2020Review
- Intestinal Absorption of Bile Acids in Health and Disease.Comprehensive Physiology · 2019Review
- GutSelf: Interindividual Variability in the Processing of Dietary Compounds by the Human Gastrointestinal Tract.Molecular nutrition & food research · 2019Review
- Associations of chronic diarrhoea with non-alcoholic fatty liver disease and obesity-related disorders among US adults.BMJ open gastroenterology · 2019Article
- Update on Bile Acid Malabsorption: Finally Ready for Prime Time?Current gastroenterology reports · 2018Review
- Pros and Cons of the SeHCAT Test in Bile Acid Diarrhea: A More Appropriate Use of an Old Nuclear Medicine Technique.Gastroenterology research and practice · 2018Review
- Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea.Alimentary pharmacology & therapeutics · 2017Article
- Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea.Gastroenterology · 2017Review
- Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT-777: role of submucosal neurons.Neurogastroenterology and motility · 2016Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The pathobiology of irritable bowel syndrome (IBS) is multifaceted. We aimed to identify candidate genes predisposing to quantitative traits in IBS. In 30 healthy volunteers, 30 IBS-constipation, and 64 IBS-diarrhea patients, we measured bowel symptoms, bile acid (BA) synthesis (serum 7α-hydroxy-4-cholesten-3-one and FGF19), fecal BA and fat, colonic transit (CT by scintigraphy), and intestinal permeability (IP by 2-sugar excretion). We assessed associations of candidate genes controlling BA metabolism (KLB rs17618244 and FGFR4 rs351855), BA receptor (GPBAR1 rs11554825), serotonin (5-HT) reuptake (SLC6A4 through rs4795541 which encodes for the 44-bp insert in 5HTTLPR), or immune activation (TNFSF15 rs4263839) with three primary quantitative traits of interest: colonic transit, BA synthesis, and fecal BA excretion. There were significant associations between fecal BA and CT at 48 h (r = 0.43; P < 0.001) and IP (r = 0.23; P = 0.015). GPBAR1 genotype was associated with CT48 (P = 0.003) and total fecal BA [P = 0.030, false detection rate (FDR) P = 0.033]. Faster CT48 observed with both CC and TT GPBAR1 genotypes was due to significant interaction with G allele of KLB, which increases BA synthesis and excretion. Other univariate associations (P < 0.05, without FDR correction) observed between GPBAR1 and symptom phenotype and gas sensation ratings support the role of GPBAR1 receptor. Associations between SLC6A4 and stool consistency, ease of passage, postprandial colonic tone, and total fecal BA excretion provide data in support of future hypothesis-testing studies. Genetic control of GPBAR1 receptor predisposing to pathobiological mechanisms in IBS provides evidence from humans in support of the importance of GPBAR1 to colonic motor and secretory functions demonstrated in animal studies.
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