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

Abstract

P ϭ 0.028). There was significant association of CNR1 rs806378 (P ϭ 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 ϭ 0.025), but not pain; the strongest associations for gas ratings were in IBS-D (P ϭ 0.002) and IBSalternating (P ϭ 0.025) subgroups. For CNR1 (AAT)n, gene-byphenotype interactions were observed for colonic transit at 24 (P ϭ 0.06) and 48 h (P ϭ 0.002) and gas (P ϭ 0.046, highest for IBS-D, P ϭ 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.

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

“…In our prior study, we detected that rs376618 was not in Hardy-Weinberg equilibrium (P ϭ 0.048) (8), and, in the present study, it was present in similar proportions in IBS-D (15/16) and controls (49/50).…”

“…FGFR4 rs351855 was previously identified as a characteristic involved significantly with KLB rs17618244, which was associated with colonic transit at 24 h in the IBS-D subgroup (8). In the present study, rs351855 was not significantly associated with symptom phenotype (P ϭ 0.30), and there was not an association with colonic transit at 24 h (P ϭ 0.81) and at 48 h (P ϭ 0.76).…”

Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview

“…Other research has focused on genes related to immune regulation and epithelial barrier function [32], 5-HT signaling [33, 34], cannabinoid receptors [35], and bile acid (BA) synthesis [36, 37], with varying results. The largest genome-wide association study to date in IBS contained only around 5,500 individuals [38], which compared with 30 to 40,000 in some inflammatory bowel disease cohorts [39, 40], limits the ability to draw firm conclusions.…”

The Role of the Endocannabinoid System in the Brain–Gut Axis

“…These actions prompted detailed studies of the role of the ECS in the control of motility and specifically in IBS (Figure 6). Variants of the CNR1 and FAAH genes have been observed in patients with diarrhea-predominant and alternating forms of IBS 82-84 . Levels of FAAH mRNA are reduced in intestinal tissues of patients with constipation-predominant IBS 85 .…”