Serotonin transporter gene (SLC6A4) polymorphism in patients with irritable bowel syndrome and healthy controls

J Gastrointestin Liver Dis. 2012 Mar;21(1):31-8.


Background: Polymorphisms in serotonin re-uptake transporter (SERT or SLC6A4) gene may play role in disturbance in gut function in irritable bowel syndrome (IBS). The aim of this study was to evaluate the association between SLC6A4 polymorphism of SERT-P and serotonin (5-hydroxytryptamine, 5-HT) concentration in IBS as compared with controls.

Methods: 150 patients with IBS (Rome-III criteria) and 252 controls were subjected to SLC6A4 genotyping. 5-HT was measured in the rectal biopsy of patients only.

Results: Patients and controls were age and gender-matched. Patients were classified into D-IBS: 79 (52%), C-IBS: 52 (35%) and A-IBS: 19 (13%). SLC6A4 polymorphism differed in IBS and controls [genotypes s/s, 89 (59%), l/s, 44 (29%), and l/l, 17 (12%) vs. s/s, 92 (37%), l/s, 114 (45%), and l/l, 46 (18%), p<0.001]. SLC6A4 s/s genotype was commoner in D-IBS than C-IBS, A-IBS and controls (p<0.001). 5-HT level was higher in D-IBS than A-IBS and C-IBS (154.7±37.1 vs. 112.4±24.6 vs. 104.3±23.7-pmol/mL, p<0.001) and in s/s than l/s and l/l genotypes (151.1±37.3 vs. 105.0±20.9 vs. 100.9±28.0-pmol/mL, p<0.001). IBS with s/s genotype more often had abdominal pain than l/s and l/l [78/89 (87.6%) vs. 19/44 (43%) vs. 5/17 (29%), p<0.001]. 5-HT level was higher among IBS patients with abdominal pain and diarrhea than without (142.9±39.4 vs. 108.4±28.9-pmol/mL, p<0.001) and (140.2±41.3-pmol/mL vs. 121.3±35.0-pmol/mL, p=0.003).

Conclusion: The frequency of SLC6A4-polymorphism and higher levels of 5-HT were significantly associated with IBS, particularly in patients with diarrhea and abdominal pain, suggesting that SLC6A4 is a potential candidate gene involved in the pathogenesis of IBS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Biomarkers / metabolism
  • Case-Control Studies
  • Female
  • Genetic Markers
  • Genotyping Techniques
  • Humans
  • Intestinal Mucosa / metabolism
  • Irritable Bowel Syndrome / genetics*
  • Irritable Bowel Syndrome / metabolism
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Rectum / metabolism
  • Sequence Deletion
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • Biomarkers
  • Genetic Markers
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin