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.
- Author:
Yu ZHANG
1
;
Yaoyao LI
;
Zhenfeng HAO
;
Xiangming LI
;
Ping BO
;
Weijuan GONG
Author Information
- Publication Type:Original Article
- Keywords: Female; Functional gastrointestinal disorders; MicroRNA-510; Receptors; Serotonin; 5-HT3
- MeSH: Asian Continental Ancestry Group*; Binding Sites; Colon; Diarrhea*; Dyspepsia; Female; Gastrointestinal Diseases; Genotype; HT29 Cells; Humans; Immunohistochemistry; Intestines; Irritable Bowel Syndrome*; Luciferases; MicroRNAs; Mucous Membrane; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Serotonin*
- From:Journal of Neurogastroenterology and Motility 2016;22(2):272-281
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: The 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. METHODS: Polymerase 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. RESULTS: Genotyping 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: The single-nucleotide polymorphisms rs56109847 led to reduced microRNA binding and overexpression of the target gene in intestinal cells, thereby increasing IBS-D risk in the Chinese Han population. The decreased expression of miR-510 might contribute to IBS-D.
