Association of serotonin transporter promoter polymorphism (5-HTTLPR) with orocecal transit time in irritable bowel syndrome

Arbab Sikander; Satya Vati Rana; Saroj Kant Sinha; Kaushal Kishor Prasad; Sunil K Arora

doi:10.1007/s12664-022-01280-1

Association of serotonin transporter promoter polymorphism (5-HTTLPR) with orocecal transit time in irritable bowel syndrome

Indian J Gastroenterol. 2022 Dec;41(6):610-617. doi: 10.1007/s12664-022-01280-1. Epub 2022 Dec 27.

Authors

Arbab Sikander¹, Satya Vati Rana^{2

3}, Saroj Kant Sinha³, Kaushal Kishor Prasad³, Sunil K Arora⁴

Affiliations

¹ Department of Biochemistry, Islamiah College (Autonomous), College Road, New Town, Vaniyambadi, Tirupathur District, 635 752, India. arbab_bio1@yahoo.com.
² Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, 249 202, India.
³ Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
⁴ Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.

PMID: 36573962
DOI: 10.1007/s12664-022-01280-1

Abstract

Background: Irritable bowel syndrome (IBS) is a multifactorial disorder with altered intestinal motility, secretion, and sensation. Serotonin (5-HT) stimulates gut motility and alters serotonin signaling that may lead to both intestinal and extraintestinal symptoms in IBS.

Aim: The aim of this study was to examine the association of serotonin transporter gene promoter polymorphism (5-HTTLPR) in IBS with orocecal transit time (OCTT) measured by lactulose hydrogen breath test.

Method: This prospective case-control study included 151 IBS patients (mean±SD 37.4±11.6 years, median 36, range 19-68). Ninety-two patients were diarrhea-predominant IBS (D-IBS), 44 constipation-predominant IBS (C-IBS), 15 alternating diarrhea and constipation IBS (M-IBS), and 100 healthy controls (mean±SD 37.2±11.4 years, median 36, range 20-64 years). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based method. 5-HT levels were measured by enzyme-linked immunosorbent assay (ELISA). Orocecal transit time (OCTT) was measured by a non-invasive lactulose hydrogen breath test. OCTT was also compared with respect to 5-HTTLPR genotypes in different IBS phenotypes.

Results: Serum serotonin levels were significantly higher in overall IBS patients (152±77 ng/mL, p<0.001), D-IBS (184±76 ng/mL, p<0.001), compared to healthy controls (129±56 ng/mL). There was no difference in 5-HT levels between C-IBS (124±53 ng/mL) and controls. In the case of M-IBS, 5-HT levels were (88±49 ng/mL p<0.05) significantly lower than that of controls. OCTT was significantly shorter in D-IBS patients (95±36 min) as compared to controls (112±41 min). In contrast, C-IBS showed significantly prolonged OCTT (136±54 min). There was a significant difference in OCTT between D-IBS and C-IBS patients (p<0.001). There was no significant association found between OCTT and 5-HTTLPR.

Conclusions: Serum serotonin concentrations were increased in D-IBS compared to controls and C-IBS. OCTT was shorter in D-IBS and delayed in C-IBS patients. There was no association of 5-HTLPR polymorphism with OCTT.

Keywords: Function bowel disorder; Gastrointestinal motility; Hydrogen breath test; Orocecal transit time; Serotonin; Serotonin transporter promoter polymorphism; Small bowel motility.

MeSH terms

Case-Control Studies
Constipation
Diarrhea / genetics
Humans
Hydrogen / metabolism
Irritable Bowel Syndrome* / genetics
Lactulose
Polymorphism, Genetic
Serotonin
Serotonin Plasma Membrane Transport Proteins* / genetics

Substances

Hydrogen
Lactulose
Serotonin
Serotonin Plasma Membrane Transport Proteins
SLC6A4 protein, human