Association of cannabinoid type 1 receptor and fatty acid amide hydrolase genetic polymorphisms in <scp>C</scp>hinese patients with irritable bowel syndrome

Jiang, Yingjie; Nie, Yongzhan; Li, Yuyuan; Zhang, Long

doi:10.1111/jgh.12513

Cited by 25 publications

(15 citation statements)

References 43 publications

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“…In line with a possible role of CNR1 variants in the development of IBS symptoms, allele frequencies of AAT triplet repeats in CNR1 were observed to be associated with IBS in a study of a Korean population . Similar results, namely the detection of eight CNR1 alleles with AAT triplet repeats, were reported in a Chinese IBS cohort, whereas no association could be detected between C385A FAAH polymorphism and IBS pathogenesis . Interestingly, FAAH activity was recently determined in whole colon samples from patients who underwent colectomy for slow transit constipation …”

Section: Cannabinoids and Functional Bowel Disorderssupporting

confidence: 52%

“…69 Similar results, namely the detection of eight CNR1 alleles with AAT triplet repeats, were reported in a Chinese IBS cohort, whereas no association could be detected between C385A FAAH polymorphism and IBS pathogenesis. 70 Interestingly, FAAH activity was recently determined in whole colon samples from patients who underwent colectomy for slow transit constipation. 71 The results revealed a strong decrease in activity in these patients as compared to individuals free of transit dysfunction.…”

Section: Ibs: Genetic Variations and The Ecsmentioning

confidence: 99%

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The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

Hasenoehrl

Taschler

Storr

et al. 2016

Neurogastroenterology Motil

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Section: Cannabinoids and Functional Bowel Disorderssupporting

confidence: 52%

Section: Ibs: Genetic Variations and The Ecsmentioning

confidence: 99%

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

Hasenoehrl

Taschler

Storr

et al. 2016

Neurogastroenterology Motil

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“…5 Camilleri 5 discovered that SERT was lowly expressed in the local intestinal tract of IBS-D patients, which resulted in elevated intestinal 5-HT levels and correlated with IBS-D susceptibility. 5 Cannabinoid receptor 1 (CNR1) is associated with symptom phenotype, pain perception, inhibition of nerve transmission, and colonic transit in IBS-D. 6 Inhibition of CNR1 expression may enhance visceral sensitivity and susceptibility to ulcerative colitis. 7 Furthermore, CNR1 inhibits GI motility in the enteric nervous system, mainly by inhibiting contractile neurotransmitter release.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

Hou

Huang

Zhang

et al. 2018

J Neurogastroenterol Motil

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Background/AimsMicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown.MethodsWe established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats.ResultsThe IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs.ConclusionsThis study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

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“…6,7 Recent studies on the familial aggregation of patients with FGID have indicated that hereditary factors may contribute to susceptibility to FGID. 6,8,9 MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by binding to the 3′-untranslated region (3′-UTR) of the messenger RNA (mRNA) of the target gene. 10 MicroRNAs are involved in the pathogenesis of FGID.…”

Section: Introductionmentioning

confidence: 99%

Association of the Serotonin Receptor 3E Gene as a Functional Variant in the MicroRNA-510 Target Site with Diarrhea Predominant Irritable Bowel Syndrome in Chinese Women

Zhang

Hao

et al. 2016

J Neurogastroenterol Motil

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Background/AimsThe functional variant (rs56109847) in the 3′-untranslated regions (3′-UTR) of the serotonin receptor 3E (HTR3E) gene is associated with female diarrhea predominant irritable bowel syndrome (IBS-D) in British populations. However, the relationship of the polymorphism both to HTR3E expression in the intestine and to the occurrence of Chinese functional gastrointestinal disorders has yet to be examined. MethodsPolymerase chain reaction amplification and restriction fragment length polymorphism analyses were employed to detect polymorphisms among Chinese Han women, particularly 107 patients with IBS-D, 99 patients with functional dyspepsia (FD), 115 patients with mixed IBS and 69 patients with IBS-D + FD. We also assessed microRNA-510 (miR-510) and HTR3E expression in human colonic mucosal tissues with immunohistochemistry and other methods. Dual-luciferase reporter assays were conducted to examine the binding ability of miR-510 and HTR3E 3′-UTR. ResultsGenotyping data showed the variant rs56109847 was significantly associated with IBS-D, but not with FD, mixed-IBS, or FD + IBS-D. HTR3E was abundantly expressed around the colonic mucosal glands but less expressed in the stroma. miR-510 expression decreased, whereas HTR3E expression increased in the colonic mucosal tissue of patients with IBS-D compared with those in controls. HTR3E expression was significantly higher in patients with the GA genotype than that in patients with the GG genotype. The single-nucleotide polymorphisms disrupted the binding site of miR-510 and significantly upregulated luciferase expression in HEK293 and HT-29 cells. Conclusions

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Association of cannabinoid type 1 receptor and fatty acid amide hydrolase genetic polymorphisms in Chinese patients with irritable bowel syndrome

Abstract: The variation in the (AAT)n repeat of the CNR1 gene conferred an increased risk for developing IBS, while rs324420 (C385) in the FAAH gene was not associated with IBS pathogenesis.

Cited by 25 publications

References 43 publications

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

Association of the Serotonin Receptor 3E Gene as a Functional Variant in the MicroRNA-510 Target Site with Diarrhea Predominant Irritable Bowel Syndrome in Chinese Women

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