Serotonin Transporter Gene Polymorphism And SERT Expression Of Colon Mucosa In Irritable Bowel Syndrome

Objective Irritable bowel syndrome (IBS) is a frequent disorder of the lower gastrointestinal tract with characteristic abdominal pain or discomfort accompanied by altered bowel habits, including alterations in stool frequency and/or form or appearance, especially disordered defecation. IBS can be sub-typed according to the predominant bowel movement type:IBS with constipation (C-IBS), IBS with diarrhea (D-IBS), and IBS with alternating symptoms of both constipation and diarrhea (A-IBS). Despite many researches, the complicated and multifactorial pathogenesis underlying IBS is not completely understood. Recently, a great number of researches has shown that a serotonin transporter (SERT) gene polymorphism plays an important role in the etiology of IBS. This polymorphism might regulate the translation and expression of SERT in the gut and is therefore an attractive candidate gene for IBS. The purpose of this study is to investigate how SERT gene polymorphism influences the SERT mRNA transcription efficiency and espression to regulate5-HT, which affects clinical symptoms in IBS patients ultimately. What is more, the observation of ultrastructural changes in intestinal mucosa of patients with IBS could help us to clear the possible effects on the pathogenesis of IBS to guide clinical treatment.Methods The first part:SERT gene polymorphism was assessed by polymerase chain reaction (PCR) on DNA chains obtained from blood of patients. We measured SERT mRNA transcription efficiency using RT-PCR. The second part:The expression of5-HT-positive cell and SERT were respectively detected by immunohistochemistry and in situ hybridization in different IBS subtypes. The third part:Ultrastructural changes in the intestinal mucosa of patients with IBS.Statistical analysis was carried out using SPSS17.0. Numerical values are expressed as the mean±SD. Genotype and allele frequency of the SERT gene polymorphism can be expressed by%, and χ2test was used to analyze the relationships between IBS patients and the control and the relationships among the IBS subtypes. One-way analysis of variance (ANOVA) and a post-hoc (Dunnett’s T3and Dunnett’s C) were used to compare SERT mRNA. χ2test was also analyzed5-HT-positive cell and SERT in the intestinal mucosa of patients with IBS.Results SERT gene polymorphism could affect SERT mRNA transcription efficiency, which regulates5-HT to relate to Somatic Symptoms of IBS. Firstiy, the L/L genotype frequencies in C-IBS were significantly higher than those in control, D-IBS and A-IBS, whereas the S/S genotype frequency in D-IBS was significantly higher than those in C-IBS and A-IBS. SERT gene mRNA transcriptional efficiency of the L/L genotype in the C-IBS was higher than those in the L/S genotype and S/S genotype. SERT mRNA transcription efficiency in C-IBS was higher than those was higher than those and control. Secondly, the expression of5-HT-positive cell decreased successively in D-IBS, A-IBS, control and C-IBS. But the positive rate of SERT mRNA increased successively in D-IBS, A-IBS, control and C-IBS. Thirdly, the ultrastructural changes including chalice cell, neuroendocrin cell, plasma cell and mast cell in the intestinal mucosa of patients with IBS could have a potential effect on neuro-immunologic mechanism and visceral hypersensitivity of IBS.Conclusions SERT gene polymorphism can determine SERT mRNA transcription efficiency so as to regulate5-HT expression, which ultimately affects somatic symptoms of IBS. What is more, the ultrastructural changes in the intestinal mucosa of patients with IBS have a potential effect on neuro-immunologic mechanism, visceral hypersensitivity and intestinal infection of IBS.