Serotonin Transporter Gene Polymorphism In Functional Constipation, Functional Diarrhea And Irritable Bowel Syndrome

Background and Aims: Serotonin (5-HT) , a key mediator of the brain-gut connection, modulates sensorimotor functions in the digestive tract. After releasing from the enterochromaffin cells and enteric neurons, it undergoes reuptake by the serotonin transporter (SERT, 5-HTT, or SLC6A4) expressed in enterocytes and enteric serotonergic neurons. There are two important polymorphic sites in the SERT gene: variable number tandem repeats (VNTRs) in the second intron, and SERT gene-linked polymorphic region [5-HTTLPR], which might influence the transcription efficiency of SERT gene and the stability of the mRNA transcripted. The aim of the study was to evaluate the relationshipbetween SERT gene polymorphism and some functional bowel disorders. Patients and methods: The study group comprised 142 patients (31 with functional constipation, 30 with functional diarrhea, 30 with constipation predominant IBS, 32 with diarrhea predominant IBS, 19 with alternating diarrhea and constipation IBS) with functional bowel disorders. The control group comprised 48 volunteers who were ruled out functional bowel disorders and any other structural or biochemical diseases. SERT gene polymorphism was assessed by polymerase chain reaction on DNA chains obtained from leukocytes in serumor colonoscopic biopsy samples. Results:1. The 10/12 genotype frequency of VNTRs alleles in FC was found at a significantly higher level than that in control.2. The L/L genotype frequencies in FC and C-IBS were significantly higher than those in FDi, D-IBS and A-IBS, whereas the S/S genotype frequency in FC was significantly lower than those in FDi, C-IBS, D-IBS and A-IBS. The L allele frequency in FC was significantly higher than those in other groups, and the verylong allele (VL), extra long allele (XL) and extra extra long allele (XXL) were also found in FC and control.3. The frequencies of 12/12-L/L and 12/10-L/L genotypes in FC group were significantly higher than that in control, whereas the 12/12-S/S genotypes were absent in FC. The frequencies of 12/12-L/S genotypes in FDi, D-IBS and A-IBS were significantly higher than that in FC. The frequencies of 12/12-L/L and 12/12-S/S genotypes in C-IBS were significantly higher than that in control. Conclusions:1. The relationship between STin2.12/10 and FC was found.2. The presence of L/L genotype in patients with FBDs carries an increased risk of FC and C-IBS, whereas the presence of the L/S genotype carries an increased risk of FDi, D-IBS and A-IBS, and the presence of S/S genotype might be a protective factor of FC.3. The presence of 12112-L/L or 12110-L/L genotypes in patients with FBDs carries an increased risk of FC, and the presence of the 12/12-S/S genotype might be a protective factor of FC, and the presence of 12/12-L/S genotype might carries an increased risk of FDi, D-IBS and A-IBS.