scholarly journals Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits

2013 ◽  
Vol 304 (5) ◽  
pp. G553-G560 ◽  
Author(s):  
Michael Camilleri ◽  
Gururaj J. Kolar ◽  
Maria I. Vazquez-Roque ◽  
Paula Carlson ◽  
Duane D. Burton ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Small Bowel ◽  
Quantitative Traits ◽  
Cannabinoid Receptors ◽  
Genetic Model ◽  
Functional Gastrointestinal Disorders ◽  
Colonic Transit ◽  
N Gene ◽  
Irritable Bowel ◽  
Symptom Phenotype

Genetic variations in metabolism of endocannabinoids and in CNR1 (gene for cannabinoid 1 receptor) are associated with symptom phenotype, colonic transit, and left colon motility in irritable bowel syndrome (IBS). Our aim was to evaluate associations between two variations in CNR1 genotype (rs806378 and [AAT]n triplets) with symptom phenotype, small bowel and colonic transit, and rectal sensations in 455 patients with IBS and 228 healthy controls. Small bowel and colonic transit were measured by scintigraphy, rectal sensation by isobaric distensions. Associations with genotype were assessed by χ2 test (symptom phenotype) and ANCOVA (quantitative traits) based on a dominant genetic model. Significant association of CNR1 rs806378 (but not CNR1 [AAT]n) genotype and symptom phenotype was observed (χ2 P = 0.028). There was significant association of CNR1 rs806378 ( P = 0.014; CC vs. CT/TT) with colonic transit in IBS-diarrhea (IBS-D) group; the TT group had the fastest colonic transit at 24 and 48 h. There was significant overall association of CNR1 rs806378 with sensation rating of gas ( P = 0.025), but not pain; the strongest associations for gas ratings were in IBS-D ( P = 0.002) and IBS-alternating ( P = 0.025) subgroups. For CNR1 (AAT)n, gene-by-phenotype interactions were observed for colonic transit at 24 ( P = 0.06) and 48 h ( P = 0.002) and gas ( P = 0.046, highest for IBS-D, P = 0.034), but not pain sensation; the strongest association with transit was in controls, not in IBS. These data support the hypothesis that cannabinoid receptors may play a role in control of colonic transit and sensation in humans and deserve further study as potential mediators or therapeutic targets in lower functional gastrointestinal disorders.

scholarly journals Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit

2014 ◽  
Vol 306 (1) ◽  
pp. G13-G26 ◽  
Author(s):  
Michael Camilleri ◽  
Eric W. Klee ◽  
Andrea Shin ◽  
Paula Carlson ◽  
Ying Li ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Principal Components Analysis ◽  
Principal Components ◽  
Quantitative Traits ◽  
Colonic Transit ◽  
Fecal Bile Acids ◽  
Components Analysis ◽  
Irritable Bowel ◽  
Symptom Phenotype

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.

scholarly journals Tu1425 Relationship of HLA-DQ Genotype With Small Bowel and Colonic Transit and Permeability, and Small Bowel Inflammation in Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)

2012 ◽  
Vol 142 (5) ◽  
pp. S-829
Author(s):  
Maria I. Vazquez-Roque ◽  
Michael Camilleri ◽  
Thomas C. Smyrk ◽  
Joseph A. Murray ◽  
Jessica O'Neill ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Small Bowel ◽  
Colonic Transit ◽  
Hla Dq ◽  
Irritable Bowel ◽  
Relationship Of

scholarly journals Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion

2014 ◽  
Vol 307 (5) ◽  
pp. G508-G516 ◽  
Author(s):  
Michael Camilleri ◽  
Andrea Shin ◽  
Irene Busciglio ◽  
Paula Carlson ◽  
Andres Acosta ◽  
...  
Keyword(s):  
Bile Acid ◽  
Candidate Genes ◽  
Animal Studies ◽  
Quantitative Traits ◽  
Colonic Transit ◽  
Colonic Motor ◽  
Quantitative Changes ◽  
Irritable Bowel ◽  
Symptom Phenotype

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.

Alosetron retards small bowel and overall colonic transit in diarrhea-predominant irritable bowel syndrome (D-IBS)

2000 ◽  
Vol 118 (4) ◽  
pp. A848 ◽  
Author(s):  
Blanca Viramontes ◽  
Sanna McKinzie ◽  
Darrell S. Pardi ◽  
Duane Burton ◽  
George M. Thomforde ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Small Bowel ◽  
Colonic Transit ◽  
Irritable Bowel

Prucalopride accelerates small bowel and colonic transit in patients with chronic functional constipation (FC) or constipation-predominant irritable bowel syndrome (C-IBS)

2000 ◽  
Vol 118 (4) ◽  
pp. A845 ◽  
Author(s):  
Michael Camilleri ◽  
Sanna McKinzie ◽  
Duane Burton ◽  
George M. Thomforde ◽  
Alan R. Zinsmeister ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Small Bowel ◽  
Functional Constipation ◽  
Colonic Transit ◽  
Irritable Bowel

scholarly journals PSYCHOLOGICAL FEATURES OF CHILDREN WITH IRRITABLE BOWEL SYNDROME

2020 ◽  
Vol 20 (1) ◽  
pp. 91-95
Author(s):  
A.V. Zubarenko ◽  
V.V. Luzan ◽  
T.Yu. Kravchenko ◽  
G.K. Kopiyka ◽  
V.I. Martyuk
Keyword(s):  
Irritable Bowel Syndrome ◽  
Emotional Disorders ◽  
Functional Gastrointestinal Disorders ◽  
Psychological Disorders ◽  
Gastrointestinal Disorders ◽  
Depressed Type ◽  
Clinical Variant ◽  
Irritable Bowel ◽  
Psychological Features ◽  
The Brain

Functional gastrointestinal disorders are considered as a clinical variant of the interaction between psychosocial factors and gastrointestinal tract physiology implemented through the "brain - intestine" axis. The purpose of the study was to investigate psychological peculiarities of children with irritable bowel syndrome. The study included 68 children aged from 14 to 18 years with the confirmed diagnosis of irritable bowel syndrome. To determine the type of character accentuation, the Schmishek -Leonhard test questionnaire (child version) was used. The SCL-90-R test questionnaire (by L. Derogatis method) was applied to determine psycho-emotional disorders. The study has found out the majority of patients have certain psycho-emotional disorders. The group of children with irritable bowel syndrome, who were experiencing constipation, more frequently demonstrated an emotional type of character accentuation and a somatized and depressed type of psychological disorders. The patients with irritable bowel syndrome and diarrhoea had cycloid and demonstrative types of character accentuation and demonstrated an anxious type according to the questionnaire. The patients with mixed bowel rhythms exhibited features of a cycloid, emotional, and pedantic type of character accentuation. Depression, anxiety, somatised types were reported as manifestations of psychological disorders.

Genetic Susceptibility to Inflammation is Associated With Colonic Transit and Other Intermediate Phenotypes in Irritable Bowel Syndrome

2011 ◽  
Vol 140 (5) ◽  
pp. S-152 ◽  
Author(s):  
Michael Camilleri ◽  
Paula Carlson ◽  
Sanna McKinzie ◽  
Marco Zucchelli ◽  
Mauro D'Amato ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Genetic Susceptibility ◽  
Colonic Transit ◽  
Intermediate Phenotypes ◽  
Irritable Bowel
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