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, Yu; Li, Yaoyao; Hao, Zhenfeng; Li, Xiangming; Bo, Ping; Gong, Weijuan

doi:10.5056/jnm15138

Cited by 17 publications

(14 citation statements)

References 27 publications

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“…Therefore, we performed a meta-analysis to estimate the association between HTR3A and HTR3E polymorphisms and the risk for IBS-D. To the best of our knowledge, this is the first meta-analysis to explore the relationships between HTR3A and HTR3E gene polymorphisms and IBS-D susceptibility. Five case-control studies [ 11 – 14 , 26 ] with a total of 1,287 IBS-D patients and 1,418 healthy controls were included in our meta-analysis, which was giving a greater power to detect IBS-D risk associated with HTR3A and HTR3E gene polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic predisposition has been demonstrated in classical family/twin studies and epidemiological surveys, but unequivocal susceptibility genes have yet to be identified [ 2 , 10 ]. Recently, several genetic association studies identified the serotonin receptor type 3 (5-HT 3 ) subunit genes HTR3A and HTR3E polymorphisms as being significantly associated with IBS ( particularly IBS-D) [ 11 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the associations between these two HTR3 polymorphisms ( HTR3A and HTR3E ) and the risk of IBS-D have been intensively investigated. However, the community is still unable to reach a consensus, particularly regarding the data from different ethnicities and genders [ 11 – 14 , 26 ]. Such inconsistencies are generally due to ethnic differences or variations in sample size.…”

Section: Introductionmentioning

confidence: 99%

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HTR3A and HTR3E gene polymorphisms and diarrhea predominant irritable bowel syndrome risk: evidence from a meta-analysis

Guan

Cai

et al. 2017

Oncotarget

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Several studies have reported an association between serotonin receptor type 3 (5-HT3) subunit genes HTR3A (rs1062613) and HTR3E (rs62625044) and diarrhea predominant irritable bowel syndrome (IBS-D). However, the results remain inconclusive and controversial, particularly for the data derived from different ethnicities and genders. Therefore, we performed a meta-analysis to evaluate this association. All eligible case-control studies that met the search criteria were retrieved from multiple databases, and five case-control studies were included for detailed evaluation. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations of HTR3A (rs1062613) and HTR3E (rs62625044) polymorphisms with IBS-D risk. Our results revealed statistically significant associations of the HTR3A (rs1062613, C/T) polymorphism with a decreased risk of IBS-D in all genetic models. Additionally, the HTR3E (rs62625044, G/A) polymorphism was also found to be significantly associated with a decreased risk of IBS-D in the allele and recessive models. Subgroup analysis revealed that these associations held true especially for Asians and female. In conclusion, this meta-analysis suggested that the C allele of HTR3A (rs1062613) and the G allele of HTR3E (rs62625044) are associated with a decreased risk of IBS-D.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HTR3A and HTR3E gene polymorphisms and diarrhea predominant irritable bowel syndrome risk: evidence from a meta-analysis

Guan

Cai

et al. 2017

Oncotarget

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“…Of note, none of the miRNAs detected to be deregulated in IBS‐D in our study did overlap with any miRNAs that have previously been reported in IBS. This might be attributed to gut region‐ and/or serum‐specific differences and different etiopathology since all studies but one were from non–PI‐IBS cases 17‐26,28,29 . In line with the different structure and function of the proximal and distal gut, previously differential expression profiles of miRNAs in small versus large intestine have been described that might also contribute to discrepancies in study findings 40 .…”

Section: Discussionmentioning

confidence: 95%

Comparative expression profiling in the intestine of patients with Giardia‐induced postinfectious functional gastrointestinal disorders

Martínez

Lasitschka

Thöni

et al. 2020

Neurogastroenterology Motil

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Background A Giardia outbreak in Bergen, Norway, caused postinfectious functional gastrointestinal disorders (PI‐FGIDs). Despite the devastating effects of this outbreak, it presented a unique chance to investigate the implication on the dysregulation of genetic pathways in PI‐FGID. Methods We performed the first comparative expression profiling of miRNAs and their potential target genes in microdissected rectal biopsies from 20 Giardia‐induced PI‐FGID patients vs 18 healthy controls by nCounter analysis. Subsequently, candidates were validated on protein level by immunostaining. Key Results miRNA profiling on rectal biopsy samples from 5 diarrhea‐predominant PI‐IBS cases compared to 10 healthy controls revealed differential expression in the epithelial layer. The top five regulated miRNAs were implicated in GI disease, inflammatory response, and immunological disease. Subsequently, these miRNAs and 100 potential mRNA targets were examined in 20 PI‐FGID cases and 18 healthy controls in both the mucosal epithelium and the lamina propria. Although deregulation of the selected miRNAs could not be verified in the larger sample set, mRNAs involved in barrier function were downregulated in the epithelium. Pro‐inflammatory genes and genes implicated in epigenetic modifications were upregulated in the lamina propria. Immunostaining for selected candidates on 17 PI‐FGID cases and 16 healthy controls revealed increased tryptase levels as well as a decreased and aberrant subcellular expression of occludin. Conclusions and Inferences Genes relevant to immune and barrier function as well as stress response and epigenetic modulation are differentially expressed in PI‐FGIDs and may contribute to disease manifestation.

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“…Additionally, microRNAs (miRNAs) serve as critical regulators in IBS‐D. For example, downregulation of miR‐510 can lead to IBS‐D . miR‐495, mapped in the 14q32.31 cluster, plays a crucial role not only in promoting the development of normal tissues but also regulating proliferation, apoptosis, metastasis, and chemosensitivity in cancer cells .…”

Section: Introductionmentioning

confidence: 99%

microRNA‐495 reduces visceral sensitivity in mice with diarrhea‐predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB

Fei

Wang

2020

IUBMB Life

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Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is one of the most common gastrointestinal disorders in the world, lacking effective therapies. The crucial roles of microRNAs (miRNAs) in IBS‐D have attracted increasing attention. The aim of this study is to investigate the effects of miR‐495 on the visceral sensitivity of the IBS‐D through the PI3K/AKT signaling pathway by targeting PKIB. Microarray data analysis was employed to screen the differentially expressed genes related to IBS‐D and regulatory miRNAs. Then, mice were perfused with acetic acid into the rectum to establish the IBS‐D model. Next, PKIB expression was measured in IBS‐D mice. Additionally, model mice were injected with a series of adenovirus vector to investigate the influence of miR‐495 on visceral sensitivity and rectal function in IBS‐D mice with the involvement of PKIB and PI3K/AKT signaling pathway. The IBS‐D mouse model was successfully established. PKIB was the target gene of miR‐495, and highly expressed in mice with IBS‐D. Silencing PKIB reduced visceral sensitivity in mice with IBS‐D, and overexpression of miR‐495 decreased visceral sensitivity in mice with IBS‐D by inhibiting PKIB. Moreover, miR‐495 upregulation inhibited PI3K/AKT signaling pathway through downregulating PKIB. To sum up, this study reveals that miR‐495 upregulation can reduce visceral sensitivity in IBS‐D via inhibition of PI3K/AKT signaling pathway by targeting PKIB. It suggests that miR‐495 presents a potential target for IBS‐D therapy.

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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

Cited by 17 publications

References 27 publications

HTR3A and HTR3E gene polymorphisms and diarrhea predominant irritable bowel syndrome risk: evidence from a meta-analysis

HTR3A and HTR3E gene polymorphisms and diarrhea predominant irritable bowel syndrome risk: evidence from a meta-analysis

Comparative expression profiling in the intestine of patients with Giardia‐induced postinfectious functional gastrointestinal disorders

microRNA‐495 reduces visceral sensitivity in mice with diarrhea‐predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB

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