Transcriptional Efficiency Of Serotonin Transporter Gene And Irritable Bowel Syndrome

Objective:Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorder with the characteristics of abdominal pain or discomfort accompanied by altered bowel habits such as stool frequency and/or form appearance, in particular disordered defecation. Serotonergic mechanisms are thought to play an important role in the regulation of gastrointestinal motility, visceral sensation and mood related diseases. Serotonin reuptake is controlled by the serotonin transporter(SERT) and by a common functional insertion/deletion polymorphism in the promoter region of SERT gene (5-HTTLPR).The aim of the study was to evaluate distribution characters of SERT gene polymorphism and the relationship between SERT gene polymorphism and transcription efficiency. Besides, the study assess the association between transcription efficiency and clinical symptoms.Methods:The study was divided into three parts.In the first part, we selected 58 patients (25 with diarrhea predominant IBS,23 with constipation predominant IBS,10 with alternating diarrhea and constipation IBS) with IBS according to Romeâ…¢criteria. The control group comprised 30 volunteers who were ruled out functional bowel disorders and any other structural or biochemical diseases. SERT gene polymorphism was assessed by polymerase chain reaction (PCR) on DNA chains obtained from colonoscopic biopsy samples.In the second part, we used realtime PCR method to detect mRNA transcriptional level in colon tissues.The relationship of SERT gene polymorphism and mRNA transcriptional Efficiency was studied.In the third part, patients and controls were investigated with the SCL-90 questionnaire.The relationship of mRNA transcriptional Efficiency and somatization and psychotic symptoms was studied.Results:The first part: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.The L allele frequency in C-IBS was significantly higher than those in control. The second part:Transcriptional efficiency of SERT gene mRNA in the L/L genotype was higher than those in the L/S and S/S genotype. No significant different was found in transcriptional efficiency of SERT gene mRNA between the L/S genotype and the S/S genotype.The third part:transcriptional efficiency of SERT gene mRNA in C-IBS were significantly higher than those in control, D-IBS and A-IBS.There was significant negative correlation between transcriptional efficiency of SERT gene mRNA and the factor scores of somatization,depression,anxiety,rival.Conclusion:1.The presence of L/L genotype carries an increased risk of C-IBS, whereas the presence of the S/S genotype carries an increased risk of D-IBS.2. Transcriptional efficiency of SERT gene mRNA in the L/L genotype was higher than those in L/S and S/S.3. The group had higher transcriptional efficiency of SERT gene mRNA were susceptible to C-IBS, whereas the group had lower transcriptional efficiency of SERT gene mRNA were susceptible to Mental disorders.4. SERT gene can be the candidate gene for therapy of IBS, which will have potential application prospects.