Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenergic and serotonergic mechanisms alter human gut motor functions. Genotype variation influences phenotype. Our aim was to test the hypothesis that variation in genes that control these functions is associated with gastrointestinal (GI) motor functions in humans with functional GI disorders (FGID). A database of 251 people was assembled by combining genotype data with measurements of gut transit and gastric volumes. Genetic variations evaluated were: alpha(2A) adrenergic (C-1291G), alpha(2C) (Del 332-325), 5-HT transporter (SLC6A4) and GNbeta3 (C825T). We sought associations between motor function or disease groups and genotypes, adjusting for age, gender and body mass index. Among 251 participants, 82 were healthy, 20 with irritable bowel syndrome (IBS) with mixed bowel habit, 49 with constipation-predominant IBS, 67 with diarrhoea-predominant IBS and 33 with functional dyspepsia. For all candidate genes, there was no significant association between motor function and wildtype vs non-wildtype gene status. There were significant interactions between genotype and motility phenotype, specifically GNbeta3 and alpha(2A) and gastric emptying at 4 h. Borderline associations were noted for SCL6A4 and alpha(2A) and postprandial gastric volume, and for alpha(2C) and gastric emptying at 2 h. We conclude that genotype variation may affect gastric motor functions in different FGID phenotypes. However, these candidate genes account for only a limited amount of the variance in gastric function of patients with FGID.
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PMID:An exploratory study of the association of adrenergic and serotonergic genotype and gastrointestinal motor functions. 1797 Oct 28

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including alpha2A (C-1291G), alpha2C (Del 332-325), GNbeta3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GNbeta3 was associated only with fasting GV; we did not detect associations between alpha2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GNbeta3 with fasting GV may explain, in part, the reported association of GNbeta3 with dyspepsia.
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PMID:Candidate genes and sensory functions in health and irritable bowel syndrome. 1851 40

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (gastrointestinal, GI) sensorimotor functions. We aimed to determine whether candidate ADR-SER genes affect GI responses to low dose clonidine (CLO) in humans. Forty healthy and 120 irritable bowel syndrome (IBS) participants received CLO, 0.1 mg or 0.15 mg b.i.d., for 6 days. At baseline and post-CLO, we measured: gastric volume (GV); satiation volume; rectal compliance, sensation thresholds and ratings with distensions. Genetic variations tested were: alpha2A (C-1291G), alpha2C (Del 322-325), GNbeta3 (C825T) and solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) (serotonin transporter linked polymorphic region). CLO reduced volume to satiation (P = 0.002), postprandial GV (P < 0.001), sensation threshold for pain (<0.001); CLO increased rectal compliance (P = 0.024). There were significant associations between post-CLO responses and gene variations for DeltaGV (alpha2A and SLC6A4), rectal sensation of gas (alpha2A, GNbeta3), urgency (alpha2A); and pain (GNbeta3 and SLC6A4); and rectal compliance (SLC6A4). alpha2A, GNbeta3 and SLC6A4 genotypes significantly modify responses to CLO on sensory and motor GI functions in health and IBS.
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PMID:Pharmacogenetics of low dose clonidine in irritable bowel syndrome. 1930 15

Eluxadoline has emerged as an effective treatment option for patients with diarrhea- predominant irritable bowel syndrome (IBS-D). It was approved by the Food and Drug Administration (FDA) in May 2015 for treatment of IBS-D. It is a p-opioid receptor agonist and 6-receptor antagonist that acts locally in the gastrointestinal (GI) tract. In recently published phase IlIl IBS-3001 and IBS- 3002 trials, eight patients experienced abdominal pain due to sphincter of Oddi dysfunction (SOD), and one patient had acute pancreatitis, thought to be related to eluxadoline. Here, we describe a patient with eluxadoline- induced pancreatitis, the first case we know of to be reported outside of phase Ill clinical trials. Interestingly, only patients with prior cholecystectomy developed SOD and acute pancreatitis in the IBS 3001/3002 trials which also stands true with our patient. The enthusiasm with the efficacy of this drug should not have clinicians disregard the potential adverse effects, particularly serious ones, such as acute pancreatitis. We expect more cases of eluxadoline-induced pancreatitis and SOD to be reported, and future studies should focus on better understanding this association so as to guide treatment recommendations.
Del Med J 2017 Mar
PMID:Eluxadoline-Associated Pancreatitis in a Post-Cholecystectomy Patient: A Case Report. 2989 43