Abstract

Aim To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). Methods The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. Results IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. Conclusions Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.

Highlights

  • Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder characterized by recurrent abdominal pain accompanied by changes in bowel habits: diarrhea (IBS-D), constipation (IBS-C), or mixed bowel habits (IBS-M) [1]

  • According to the diagnosis based on the Composite International Diagnostic Interview (CIDI) examination, all IBS patients were divided into four groups: without diagnosis of depressive nor anxiety disorder (n = 41, 43%), with depressive disorders only (n = 20, 21%), with anxiety disorders only (n = 25, 26%), and with comorbid depressive and anxiety disorders (n = 9, 10%)

  • Six different polymorphisms of five serotonin-related genes in the group of IBS patients with comorbid depressive or anxiety disorders diagnosed according to the diagnostic criteria of ICD-10 were investigated

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Summary

Introduction

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder characterized by recurrent abdominal pain accompanied by changes in bowel habits: diarrhea (IBS-D), constipation (IBS-C), or mixed bowel habits (IBS-M) [1]. Epidemiological data confirm high prevalence of depressive and anxiety disorders in IBS patients ranging from 40 up to 90% of subjects [2, 5,6,7,8]. Serotoninrelated gene variants have been extensively explored in IBS as well as in depressive and anxiety disorders [12,13,14,15,16]. Serotonin (5-hydroxytryptamine (5-HT)), as a main neurotransmitter of the brain-gut axis, plays a crucial role in the pathophysiology of both IBS and mental disorders [17]. Serotonin-related genetic polymorphisms have been suggested to be associated with a high comorbidity of depressive or anxiety disorders with IBS [13, 21,22,23,24]

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