Serotonin Transporter Expression And Irritable Bowel Syndrome

Objective:Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with the characteristics of abdominal pain or discomfort accompanied by altered bowel habits such as stool frequency and/or form or appearance, in particular disordered defecation. Questionare based worldwide surveies revealed a prevalence of IBS symptoms in 5% to 24% of respondents. IBS is the most common cause for referral to gastroenterologists, constituting 20% to 50% of referred patients. Patients with IBS visit the doctor more frequently, use more diagnostic tests, consume more medications, miss more workdays, have lower work productivity, and consume more overall direct costs than those without IBS. IBS influences an amplus extent the patient's quality of life. Recently, a great deal of research has shown that serotonin transporter (SERT) plays an important role in etiology of IBS. However, there is an existing controversy on that SERT how to influences the intestinal and mental symptoms. The purpose of this study is to investigate the influence of SERT gene polymophism on SERT expression and IBS symptoms as well as mental symptoms.Methods:Twenty-five patients with D-IBS,23 patients with C-IBS,10 patients with A-IBS and 30 health subjects were selected according to the Rome III criteria. Colon tissue was used for extracting genome DNA, and tandem regine in 5-HTTLPR was amplified by PCR, then, electrophoresis was utilized for discriminating polymorphism. SERT expression in colon mucosa was determined by western blotting. The study was divided into 3 parts:·The first part:Firstly, genome DNA was extracted from colon tissues.Secondly, Polymorphic region in 5-HTTLPR was amplified by PCR,then, PCR products were separated by electrophoresis to observe different genotype.·The second part:SERT protein was harvested form colon tissues, and SERT expression was determined by western blotting.·The third part:Both IBS patients and health subjects must fill self-testable scale of symptoms (SCL-90) which includes 9 factors. Then we calculated the scores.·χ2 test and analysis of variance were used to analyse relationships between IBS and control as well as among IBS subtypes as to 5-HTTLPR polymophism, colon tissue SERT expression and abdominal pain or discomfort, disordered defecation and and mental symptoms.Result: 1. Significant statistical difference was found among IBS subtype as to the distribution of 5-HTTLPR genotype (χ2=11.099, P=0.025), but No statistical significance was found between IBS patients and control (χ2=4.502, P=0.105); The frequency of L/L in C-IBS group were significantly higher than that in control(χ2=10.072, P=0.002);The frequency of L/L in C-IBS group were significantly higher than that of D-IBS and A-IBS(x2=10.072, P=0.002); The frequency of S/S were significantly higher than C-IBS,A-IBS (χ2=7.234, P=0.007); The frequency of L allele gene significantly higher than that in control (χ2=3.854, P=0.05).2. The level of SERT protein expression was variant in different genotype. The expression efficiency were significantly higher in L/L than that in L/S and S/S (P<0.01), however, there is no statistical significance between L/S and S/S(P>0.05)3. No statistical significance was found as to SERT protein expression between IBS patients and control (P>0.05). The level of protein expression in C-IBS was significantly higher than those in other groups (P<0.05), however, there is no statistical difference in protein expression between A-IBS and D-IBS (P>0.05). The level of protein expression is negatively correlated with somatization, anxiety, depression and hostility score respectively.But it uncorrelated with interpersonal sensitivity,obsessive-compulsive symptom, horror paranoia,and psychotic score.Conclusion:Polymorphism in 5-HTTLPR can determine the intestinal and mental symptoms of IBS by influence SERT protein expression.