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Digestive Diseases and Sciences

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01-11-2011 | Original Article

Serotonin Transporter and G Protein Beta 3 Subunit Gene Polymorphisms in Greeks with Irritable Bowel Syndrome

Authors: T. Markoutsaki, T. Karantanos, M. Gazouli, N. P. Anagnou, S. D. Ladas, D. G. Karamanolis

Published in: Digestive Diseases and Sciences | Issue 11/2011

Abstract

Background

Polymorphisms in the serotonin transporter (SERT) and G protein β3 subunit (GNB3) genes might contribute to the pathophysiology of irritable bowel syndrome (IBS). Association studies of SERT and GNB3 polymorphisms and IBS have shown diverse results among different populations, which might be due to subject composition differences.

Aims

The aim of the study was to assess the potential association between SERT and GNB3 polymorphisms and IBS in Greeks.

Methods

A total of 124 patients with IBS diagnosed according to the Rome III criteria and 238 healthy individuals were included in the study. SERT and GNB3 gene polymorphisms were genotyped using polymerase chain reaction-based methods.

Results

It was shown that the frequencies of the SS genotype and S allele of the serotonin transporter polymorphism were significantly associated with IBS (P = 0.0314 and P = 0.019, respectively). TT genotype and T allele frequencies of G protein β3 subunit showed also significant difference between the IBS patients and healthy controls IBS (P = 0.0163 and P = 0.0001, respectively). None of the clinical symptoms analyzed was significantly associated with the polymorphisms tested.

Conclusions

The results suggest that SERT and GNB3 gene polymorphisms might be associated with irritable bowel syndrome predisposition in Greeks.

Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491.PubMedCrossRef

Drossman DA, Dumitrascu DL. Rome III: New standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 2006;15:237–241.PubMed

Buéno L, Fioramonti J, Garcia-Villar R. Pathobiology of visceral pain: molecular mechanisms and therapeutic implications. III. Visceral afferent pathways: a source of new therapeutic targets for abdominal pain. Am J Physiol Gastrointest Liver Physiol. 2000;278:G670–G676.PubMed

Manabe N, Tanaka T, Hata J, Kusunoki H, Haruma K. Pathophysiology underlying irritable bowel syndrome—from the viewpoint of dysfunction of autonomic nervous system activity. J Smooth Muscle Res. 2009;45:15–23.PubMedCrossRef

Sikander A, Rana SV, Prasad KK. Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta. 2009;403:47–55.PubMedCrossRef

Crowell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol. 2004;141:1285–1293.PubMedCrossRef

Locke GR 3rd, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ 3rd. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc. 2000;75:907–912.PubMedCrossRef

Lembo A, Zaman M, Jones M, Talley NJ. Influence of genetics on irritable bowel syndrome, gastro-oesophageal reflux and dyspepsia: a twin study. Aliment Pharmacol Ther. 2007;25:1343–1350.PubMedCrossRef

Saito YA, Locke GR 3rd, Zimmerman JM, et al. A genetic association study of 5-HTT LPR and GNbeta3 C825T polymorphisms with irritable bowel syndrome. Neurogastroenterol Motil. 2007;19:465–470.PubMedCrossRef

10.

Camilleri M, Atanasova E, Carlson PJ, et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2002;123:425–432.PubMedCrossRef

11.

Jarrett ME, Kohen R, Cain KC, et al. Relationship of SERT polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome. Biol Res Nurs. 2007;9:161–169.PubMedCrossRef

12.

Yeo A, Boyd P, Lumsden S, et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut. 2004;53:1452–1458.PubMedCrossRef

13.

Pata C, Erdal ME, Derici E, Yazar A, Kanik A, Ulu O. Serotonin transporter gene polymorphism in irritable bowel syndrome. Am J Gastroenterol. 2002;97:1780–1784.PubMedCrossRef

14.

Lee DY, Park H, Kim WH, Lee SI, Seo YJ, Choi YC. Serotonin transporter gene polymorphism in healthy adults and patients with irritable bowel syndrome. Korean J Gastroenterol. 2004;43:18–22.PubMed

15.

Niesler B, Kapeller J, Fell C, et al. 5-HTTLPR and STin2 polymorphisms in the serotonin transporter gene and irritable bowel syndrome: effect of bowel habit and sex. Eur J Gastroenterol Hepatol. 2010;22:856–861.PubMedCrossRef

16.

Zill P, Barghai TC, Zwanzger P, et al. Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment. Neuroreport. 2000;11:1893–1897.PubMedCrossRef

17.

Virchow S, Ansorge N, Rübben H, Siffert G, Siffert W. Enhanced fMLP-stimulated chemotaxis in human neutrophils from individuals carrying the G protein beta3 subunit 825 T-allele. FEBS Lett. 1998;436:155–158.PubMedCrossRef

18.

Siffert W. G-protein beta3 subunit 825T allele and hypertension. Curr Hypertens Rep. 2003;5:47–53.PubMedCrossRef

19.

Lee HJ, Lee SY, Choi JE, et al. G protein beta3 subunit, interleukin-10, and tumor necrosis factor-alpha gene polymorphisms in Koreans with irritable bowel syndrome. Neurogastroenterol Motil. 2010;22:758–763.PubMedCrossRef

20.

Andresen V, Camilleri M, Kim HJ, et al. Is there an association between GNbeta3–C825T genotype and lower functional gastrointestinal disorders? Gastroenterology. 2006;130:1985–1994.PubMedCrossRef

21.

Holtmann G, Siffert W, Haag S, et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971–979.PubMedCrossRef

22.

Coffin B. Diagnosis of irritable bowel syndrome. Gastroenterol Clin Biol. 2009;33:S9–S16.PubMedCrossRef

23.

Park JM, Choi MG, Park JA, et al. Serotonin transporter gene polymorphism and irritable bowel syndrome. Neurogastroenterol Motil. 2006;18:995–1000.PubMedCrossRef

24.

Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996;274:1527–1531.PubMedCrossRef

25.

Collier DA, Stöber G, Li T, et al. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry. 1996;1:453–460.PubMed

26.

Sikander A, Rana SV, Sinha SK, et al. Serotonin transporter promoter variant: analysis in Indian IBS patients and control population. J Clin Gastroenterol. 2009;43:957–961.PubMedCrossRef

27.

de Vries DR, ter Linde JJ, van Herwaarden MA, Smout AJ, Samsom M. Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3). Am J Gastroenterol. 2009;104:281–285.PubMedCrossRef

Title: Serotonin Transporter and G Protein Beta 3 Subunit Gene Polymorphisms in Greeks with Irritable Bowel Syndrome
Authors: T. Markoutsaki
T. Karantanos
M. Gazouli
N. P. Anagnou
S. D. Ladas
D. G. Karamanolis
Publication date: 01-11-2011
Publisher: Springer US
Published in: Digestive Diseases and Sciences / Issue 11/2011
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-011-1726-7

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Abstract

Background

Aims

Methods

Results

Conclusions

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