title: 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.
abstract: OBJECTIVE
  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 HTR3Eexpression 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.
authors.affiliation: Department of Chinese and Western Integrative Medicine, Medical College of Yangzhou University, Yangzhou, China.|Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chinese and Western Integrative Medicine, Medical College of Yangzhou University, Yangzhou, China.|Jiangsu Coinnovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chinese and Western Integrative Medicine, Medical College of Yangzhou University, Yangzhou, China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Hao
authors.affiliation: Department of Chinese and Western Integrative Medicine, Medical College of Yangzhou University, Yangzhou, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chinese and Western Integrative Medicine, Medical College of Yangzhou University, Yangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Bo
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.|Jiangsu Coinnovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.|Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Gong
keywords: 5-HT3; Female; Functional gastrointestinal disorders; MicroRNA-510; Receptors; Serotonin