The serotonin transporter gene polymorphism (5-HTTLPR) and irritable bowel syndrome: a meta-analysis of 25 studies

Abstract

BackgroundThe results of previous studies assessing the association between the 5-HTTLPR polymorphism of serotonin transporter gene and irritable bowel syndrome (IBS) are inconsistent. The aim of this study was to clarify the association between the 5-HTTLPR mutation and the presence of IBS and its subtypes with a meta-analysis of 25 studies.MethodsA thorough search for case–control studies evaluating the association between the 5-HTTLPR polymorphism of serotonin transporter gene and the presence of IBS was carried out in four electronic databases. A meta-analysis was performed in accordance with the Cochrane Handbook for systemic reviews.ResultsA total of 25 articles with 3443 IBS cases and 3359 controls were included into our meta-analysis. No significant association was found between this polymorphism and IBS in all populations. Whereas the LL genotype was demonstrated to be a risk factor for constipation predominant IBS (IBS-C) development in the overall population (LL vs SS: OR = 1.570, 95% CI = 1.147-2.148, P = 0.005, Bon = 0.030; LL vs LS: OR = 1.658, 95% CI = 1.180-2.331, P = 0.004, Bon = 0.024; LL vs LS/SS: OR = 1.545, 95% CI = 1.187-2.012, P = 0.001, Bon = 0.006). In the analysis of different ethnicities, L allele and LL genotype were significantly associated with increased IBS-C risk in the East Asian population (L vs S: OR = 1.487, 95% CI = 1.139-1.941, P = 0.003, Bon = 0.018; LL vs SS: OR = 2.575, 95% CI = 1.741-3.808, P = 0.000, Bon = 0.000; LL vs LS: OR = 3.084, 95% CI = 2.017-4.715, P = 0.000, Bon = 0.000; LL vs LS/SS: OR = 2.759, 95% CI = 1.933-3.938, P = 0.000, Bon = 0.000), but not in the Caucasian population.ConclusionsDifferent from the conclusions of the earlier meta-analyses, the 5-HTTLPR mutation affects IBS-C but not IBS-D and IBS-M development and this effect only exists in the East Asian population but not other populations.

Association Between SLC6A4 Serotonin Transporter Gene Lainked Polymorphic Region and ADRA2A −1291C>G and Irritable Bowel Syndrome in Korea

“…Moreover, L allele and L/L genotype were significantly associated with increased IBS-C risk in the East Asian population. 30 The genotypic association between the L/L genotype and not only IBS-C but also IBS-M may result from possible misclassification of IBS-M or spectrum disorder of IBS itself. IBS-M is a highly heterogeneous due to range of symptoms that are similar to those in IBS-D and IBS-C, 31 this would cause a large proportion of patients remains IBS-M.…”

Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low‐grade inflammation in ulcerative colitis

“…Reduced SERT expression and function result in excess 5‐HT, along with motor, sensory, and secretary dysfunctions of the gut, which lead to development of diarrhea and abdominal pain associated with the pathogenesis of IBS . Furthermore, polymorphisms in the promoter region of the SERT gene influence the expression of SERT in colonic mucosa, which also plays a key role in the pathogenesis of IBS patients . Symptoms resembling IBS are known to occur in cases of IBD; thus, a common pathogenesis for IBS and IBD is possible.…”

Association of Serotonin Transporter Promoter Polymorphism (5HTTLPR) with Microscopic Colitis and Ulcerative Colitis: Time to Be AsSERTive?

“…In investigations of SERT polymorphisms in IBS, a meta-analysis of seven studies concluded that 5-HTTPLR genotypes are unrelated to IBS, while others reported evidence of an association when patients were stratified by predominant clinical symptoms [29]. The most recent meta-analysis of 25 such studies concluded that the L/L genotype of 5-HTTLPR is associated with an increased risk of developing constipation-predominant IBS (IBS-C) [30]. 5-HTTLPR genetic polymorphisms also may provide evidence for the efficacy of serotonin-based therapies for specific subtypes of IBS.…”