A serotonin transporter gene (SLC6A4) polymorphism is associated with reduced risk of irritable bowel syndrome in American and Asian population: a meta-analysis

PLoS One. 2013 Sep 19;8(9):e75567. doi: 10.1371/journal.pone.0075567. eCollection 2013.

Abstract

Aim: Association studies of serotonin transporter gene SLC6A4 I/S polymorphism and irritable bowel syndrome (IBS) have shown inconsistent and contradictory results among different populations. In the present study, meta-analysis was performed to evaluate the association between SLC6A4 I/S polymorphism and IBS susceptibility.

Methodology: Systemic assessment was performed for the published studies based on the association of SLC6A4 I/S polymorphism and IBS risk from PubMed (Medline), EMBASE search. A meta-analysis was done to appraise the said association. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model.

Results: A total of twelve studies comprising 2068 IBS cases and 2076 controls were included in this meta-analysis. Overall, no significant results were obtained for S allele carrier (S vs. I: p=0.488; OR=1.073, 95% CI=0.879 to 1.311) Co-dominant (SS vs. II; p=0.587; OR=1.112, 95% CI=0.758 to 1.631), (IS vs. II; p=0.361; OR=0.878, 95% CI=0.665 to 1.160). Similarly, dominant (SS+IS vs. II: p=0.853; OR=0.974, 95% CI=0.736 to 1.288) and recessive (SS vs. II+IS: p=0.267; OR=1.172, 95% CI=0.886 to 1.522) genetic models did not demonstrate risk. In the subgroup population based analysis, reduced risks were found in American (IS vs. II: p=0.009; OR=0.685, 95% CI=0.516 to 0.908) and Asian (SS+IS vs. II; p=0.001; OR=0.116, 95% CI=0.068 to 0.197) population. However, no risk was observed in European population.

Conclusions: This investigation clearly demonstrates that SLC6A4 (Ins/Del) polymorphism is associated with reduced risk of IBS in American and Asian population. However, future well-designed studies with stratified case control and biological characterization will be needed to validate this finding.

Publication types

  • Meta-Analysis

MeSH terms

  • Alleles
  • Asia
  • Asian People*
  • Case-Control Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Irritable Bowel Syndrome / genetics*
  • Mutation
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • United States
  • White People*

Substances

  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins

Grants and funding

The authors have no support or funding to report.