Functional polymorphism of the serotonin reuptake transporter SLC6A4 gene in various clinical variants of irritable bowel syndrome

Abstract

Rationale:Irritable bowel syndrome (IBS) is a multifactorial disease, the genetic aspect of which is being actively studied.Aim:To investigate functional polymorphism of the serotonin reuptake transporter (SERT)SLC6A4gene of various clinical variants of IBS.Materials and methods:We performed a cross-sectional single center study in 79 Caucasian patients with IBS (according to the Rome criteria IV). The patients were divided into two groups: group 1, IBS with diarrhea (IBS-D, n = 45) and group 2, IBS with constipation (IBS-C, n = 34). The control group included 59 Caucasian patients with gastrointestinal disorders without IBS. Polymorphism5-HTTLPRof theSLC6A4gene was assessed in all subjects. In group 1 patients, blood serotonin levels were measured and psychological tests were performed, including Spielberger's State / Trait Anxiety Inventory, quality of life by SF36 and GSRS, Asthenia scale, VAS scores for pain intensity.Results:Thirty-five of 45 (77.8%) patients with IBS-D carried the mutantSallele, which was significantly more frequent than in the IBS-C group (p = 0.002) and in the control group (p = 0.005). There were no statistically significant differences (p = 0.54) in the frequency of detection of the homozygousLLgenotype (normal allele) and the heteroand homozygous mutant alleles (SLandSS) genotype between the IBS-C and control patients. In the IBS-D group, a gender difference for the mutantSSallele of5-HTTLPRwas found, with significantly higher frequency in female patients (p = 0.0147). No significant gender differences in the genotype distribution between the patients with IBS-C and the control group were found. There were also no differences in blood serotonin levels in the IBS patients with various5-HTTLPRtypes (p = 0.086); they were all in the reference range. However, there was a trend towards lower serotonin levels in theLLgenotype carriers compared to those with theSS/SLpolymorphisms. The Gastroenterological inventoryGSRSdemonstrated significantly higher total score for the constipation syndrome in the patients with homozygousLL 5-HTTLPRpolymorphism, compared to that in the patients with theSS/SLgenotype (p = 0.013).Conclusion:The results may be related to lower expression of theSLC6A4gene in the carriers of the mutant allele in the5-HTTLPRpromoter and subsequent decreased rate of serotonin uptake, with resulting stimulation of the gastrointestinal tract. TheSERTpolymorphism of theSLC6A4gene is worth further investigation as a potential candidate gene in the IBS pathophysiology.