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

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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) SLC6A4 gene 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. Polymorphism 5-HTTLPR of the SLC6A4 gene 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 mutant S allele, 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 homozygous LL genotype (normal allele) and the heteroand homozygous mutant alleles (SL and SS) genotype between the IBS-C and control patients. In the IBS-D group, a gender difference for the mutant SS allele of 5-HTTLPR was 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 various 5-HTTLPR types (p = 0.086); they were all in the reference range. However, there was a trend towards lower serotonin levels in the LL genotype carriers compared to those with the SS/SL polymorphisms. The Gastroenterological inventory GSRS demonstrated significantly higher total score for the constipation syndrome in the patients with homozygous LL 5-HTTLPR polymorphism, compared to that in the patients with the SS/SL genotype (p = 0.013).

Conclusion: The results may be related to lower expression of the SLC6A4 gene in the carriers of the mutant allele in the 5-HTTLPR promoter and subsequent decreased rate of serotonin uptake, with resulting stimulation of the gastrointestinal tract. The SERT polymorphism of the SLC6A4 gene is worth further investigation as a potential candidate gene in the IBS pathophysiology.

About the authors

A. V. Pushkina

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru

Anna V. Pushkina – Assistant, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss

41 Kirochnaya ul., Saint Petersburg, 191015

Russian Federation

A. B. Avalueva

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: avalueva@mail.ru
ORCID iD: 0000-0001-6011-0998

Elena B. Avalueva – MD, PhD, Professor, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss

47–24 Piskarevsky prospekt, Saint Petersburg, 195067

Russian Federation

I. G. Bakulin

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru
ORCID iD: 0000-0002-6151-2021

Igor G. Bakulin – MD, PhD, Professor, Head of the Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss

41 Kirochnaya ul., Saint Petersburg, 191015

Russian Federation

A. A. Topanova

Almazov National Medical Research Centre

Email: fake@neicon.ru

Aleksandra A. Topanova – MD, PhD, Deputy Director of the Institute of Medical Education

2A Akkuratova ul., Saint Petersburg, 197341

Russian Federation

A. A. Murzina

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru

Alla A. Murzina – Research Fellow, Central Research Laboratory

41 Kirochnaya ul., Saint Petersburg, 191015

Russian Federation

S. I. Sitkin

North-Western State Medical University named after I.I. Mechnikov;
Almazov National Medical Research Centre;
State Research Institute of Highly Pure Biopreparations

Email: fake@neicon.ru
ORCID iD: 0000-0003-0331-0963

Stanislav I. Sitkin – Dr. med., PhD, Associate Professor, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss North-Western State Medical University named after I.I. Mechnikov; Head of Epigenetics and Metagenomics Research Group, Institute of Perinatology and Pediatrics Almazov National Medical Research Centre; Leading Research Fellow, Laboratory of Microbiology State Research Institute of Highly Pure Biopreparations

41 Kirochnaya ul., Saint Petersburg, 191015, 

2A Akkuratova ul., Saint Petersburg, 197341, 

7 Pudozhskaya ul., Saint Petersburg, 197110

Russian Federation

I. V. Lapinsky

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru

Igor V. Lapinsky – Assistant, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss

41 Kirochnaya ul., Saint Petersburg, 191015

Russian Federation

E. V. Skazyvaeva

North-Western State Medical University named after I.I. Mechnikov

Email: fake@neicon.ru

Ekaterina V. Skazyvaeva – MD, PhD, Associate Professor, Chair of Propaedeutics of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss

41 Kirochnaya ul., Saint Petersburg, 191015

Russian Federation

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Copyright (c) 2019 Pushkina A.V., Avalueva A.B., Bakulin I.G., Topanova A.A., Murzina A.A., Sitkin S.I., Lapinsky I.V., Skazyvaeva E.V.

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