ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit.
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 22 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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023.Digestion · 2024Guideline
- [Bile Acid Diarrhea].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024Review
- Association of the rs1966265 and rs351855Biomedicines · 2024Article
- Targeting the FGF19-FGFR4 pathway for cholestatic, metabolic, and cancerous diseases.Journal of internal medicine · 2024Review
- Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine.International journal of molecular sciences · 2024Review
- Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology.Nature reviews. Gastroenterology & hepatology · 2022Review
- Bile Acid Diarrhea in Adults and Adolescents.Neurogastroenterology and motility · 2022Review
- Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Article
- The Role of Bile Acids in Chronic Diarrhea.The American journal of gastroenterology · 2020Review
- Chronic diarrhea, bile acids, and Clostridia.The Journal of clinical investigation · 2020Article
- Intestinal Absorption of Bile Acids in Health and Disease.Comprehensive Physiology · 2019Review
- Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel-based chemotherapy in breast cancer patients.BMC cancer · 2018Article
- Update on Bile Acid Malabsorption: Finally Ready for Prime Time?Current gastroenterology reports · 2018Review
- Development of an AmpliSeqFrontiers in pharmacology · 2018Article
- New and emerging therapies for the treatment of irritable bowel syndrome: an update for gastroenterologists.Therapeutic advances in gastroenterology · 2016Review
- Therapeutic targeting of bile acids.American journal of physiology. Gastrointestinal and liver physiology · 2015Review
- Colonic mucosal gene expression and genotype in irritable bowel syndrome patients with normal or elevated fecal bile acid excretion.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Bile Acid diarrhea: prevalence, pathogenesis, and therapy.Gut and liver · 2015Review
- New and Emerging Treatment Options for Irritable Bowel Syndrome.Gastroenterology & hepatology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The study objectives were: to mine the complete exome to identify putative rare single nucleotide variants (SNVs) associated with irritable bowel syndrome (IBS)-diarrhea (IBS-D) phenotype, to assess genes that regulate bile acids in IBS-D, and to explore univariate associations of SNVs with symptom phenotype and quantitative traits in an independent IBS cohort. Using principal components analysis, we identified two groups of IBS-D (n = 16) with increased fecal bile acids: rapid colonic transit or high bile acids synthesis. DNA was sequenced in depth, analyzing SNVs in bile acid genes (ASBT, FXR, OSTα/β, FGF19, FGFR4, KLB, SHP, CYP7A1, LRH-1, and FABP6). Exome findings were compared with those of 50 similar ethnicity controls. We assessed univariate associations of each SNV with quantitative traits and a principal components analysis and associations between SNVs in KLB and FGFR4 and symptom phenotype in 405 IBS, 228 controls and colonic transit in 70 IBS-D, 71 IBS-constipation. Mining the complete exome did not reveal significant associations with IBS-D over controls. There were 54 SNVs in 10 of 11 bile acid-regulating genes, with no SNVs in FGF19; 15 nonsynonymous SNVs were identified in similar proportions of IBS-D and controls. Variations in KLB (rs1015450, downstream) and FGFR4 [rs434434 (intronic), rs1966265, and rs351855 (nonsynonymous)] were associated with colonic transit (rs1966265; P = 0.043), fecal bile acids (rs1015450; P = 0.064), and principal components analysis groups (all 3 FGFR4 SNVs; P < 0.05). In the 633-person cohort, FGFR4 rs434434 was associated with symptom phenotype (P = 0.027) and rs1966265 with 24-h colonic transit (P = 0.066). Thus exome sequencing identified additional variants in KLB and FGFR4 associated with bile acids or colonic transit in IBS-D.
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