Abstract
AimAssociation 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.MethodologySystemic 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.ResultsA 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.ConclusionsThis 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.
Highlights
Irritable bowel syndrome (IBS) is a predominant and common chronic gastrointestinal (GI) disorder, associated clinical manifestations are recurrent abdominal pain or discomfort, swelling, and altered bowel function, such as constipation, irregular stool frequency and alternation between these two symptoms [1,2]
We performed a PubMed (Medline), EMBASE search covering all research papers published with a combination of the following key words: “serotonin transporter protein (SERT), SLC6A4, 5-HT transporter (5-HTT) gene, Serotonin transporter gene AND irritable bowel syndrome or IBS
It is well known that IBS susceptibility is determined by the infectious agents, psychosocial and environmental factors, genetic factors play an important role in their pathogenesis [32,33]
Summary
Irritable bowel syndrome (IBS) is a predominant and common chronic gastrointestinal (GI) disorder, associated clinical manifestations are recurrent abdominal pain or discomfort, swelling, and altered bowel function, such as constipation, irregular stool frequency and alternation between these two symptoms [1,2]. The serotonin transporter protein (SERT) or 5-HT transporter (5-HTT) encoded by SLC6A4 gene (GenBank NM_001045) maps on chromosome 17q11, 1q12, mainly responsible for the reuptake of serotonin into mucosal epithelial cells and enteric neurons [6]. Abnormalities in serotonin reuptake can alter enteric serotonergic signaling, leading to gut dysfunctions that are involved in the pathophysiology of IBS [9]. These studies highlighted the significance of serotonin in IBS disease
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