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- Title
Serotonin transporter gene promoter region polymorphisms and serotonin transporter expression in the colonic mucosa of irritable bowel syndrome patients.
- Authors
Wang, Y. M.; Chang, Y.; Chang, Y. Y.; Cheng, J.; Li, J.; Wang, T.; Zhang, Q. Y.; Liang, D. C.; Sun, B.; Wang, B. M.
- Abstract
Background The role of serotonin transporter (SERT) gene polymorphism in irritable bowel syndrome (IBS) has been demonstrated. However, the expression of SERT mRNA and proteins in the colonic mucosa with different 5-HTT gene-linked polymorphic region (5-HTTLPR) genotypes remains unknown. We examined SERT mRNA and protein levels in colon biopsies from patients with different 5-HTTLPR genotypes and evaluated the links between the polymorphism and the expression levels. Methods Two hundred and fifty-four patients with IBS and 120 healthy subjects were studied. DNA samples were extracted from peripheral blood and genotyped by polymerase chain reaction (PCR). SERT mRNA and protein levels were evaluated by quantitative real time PCR and western blotting. The promoter efficiency of the serotonin transporter promoter (SERT-P) was evaluated with luciferase reporter system. Key Results The frequency of the L/L genotype in C-IBS group was significantly higher than that in the control and D-IBS. However, the S/S genotype in D-IBS was significantly higher than that in C-IBS. The transcriptional efficiency of the L/L genotype was significantly higher than that in the L/S and S/S genotype. Patients with the L/L genotype demonstrated increased production of the SERT protein when compared with L/S and S/S patients. The l variant increased SERT promoter activity by 2.43-fold when compared with the s variant. Conclusions & Inferences Polymorphism in the promoter region of the SERT gene can influence the expression of SERT mRNA and the levels of the SERT protein in the colonic mucosa, thereby playing a key role in motility-related symptoms of IBS patients.
- Subjects
SEROTONIN transporters; GENES; PROMOTERS (Genetics); IRRITABLE colon; MESSENGER RNA
- Publication
Neurogastroenterology & Motility, 2012, Vol 24, Issue 6, p560
- ISSN
1350-1925
- Publication type
Article
- DOI
10.1111/j.1365-2982.2012.01902.x