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The Association of Serotonin Transporter Genetic Polymorphisms and Irritable Bowel Syndrome and Its Influence on Tegaserod Treatment in Chinese Patients

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Abstract

The aims of this study were to investigate the relationship of genetic polymorphisms of the serotonin reuptake transporter and the clinical subtypes of irritable bowel syndrome and its influence on the efficacy of tegaserod in Chinese irritable bowel syndrome patients with constipation. Genetic polymorphisms were analyzed in 87 patients and 96 controls, then 41 irritable bowel syndrome patients with constipation received tegaserod for 4 weeks. The primary efficacy variable was the responder rate measured by Subject's Global Assessment of Relief. Secondary efficacy assessed the changes of individual symptoms weekly. There was no significant difference in genotype frequencies between the patients as a whole and the control group. The frequency of the L/L genotype in the serotonin transporter gene-linked polymorphic region was significantly higher in patients with constipation than in controls (25.0% vs. 7.3%). Responder rates to tegaserod were significantly higher in the S/S (85.0%) and L/S (70.0%) than in the L/L genotype (36.4%). All secondary variables also significantly improved in the S/S and L/S groups compared to the L/L group. This study suggests the hypothesis that individuals with the L/L genotype are vulnerable to development of irritable bowel syndrome with constipation, and patients with the L/L genotype respond poorly to treatment with a routine dose of tegaserod.

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References

  1. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA (1999) Functional bowel disorders and functional abdominal pain. Gut 45 (Suppl II):II43–II47

    Article  PubMed  Google Scholar 

  2. Cremonini F, Talley NJ (2005) Irritable bowel syndrome: epidemiology, natural history, health care seeking and emerging risk factors. Gastroenterol Clin North Am 34:189–204

    Article  PubMed  Google Scholar 

  3. Lau EM, Chen FK, Ziea ET, Chan CS, Wu JC, Sung JJ (2002) Epidemiology of irritable bowel syndrome in Chinese. Dig Dis Sci 47:2621–2624

    Article  PubMed  CAS  Google Scholar 

  4. Park MI, Cammilleri M (2005) Genetic and genotypes in irritable bowel syndrome: Implication for diagnosis and treatment. Gastroenterol Clin North Am 34:305–317

    Article  PubMed  Google Scholar 

  5. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531

    Article  PubMed  CAS  Google Scholar 

  6. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624

    Article  PubMed  CAS  Google Scholar 

  7. Greenberg BD, Tolliver TJ, Huang SJ, Li Q, Bengel D, Murphy DL (1999) Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelet. Am J Med Genet 88:83–87

    Article  PubMed  CAS  Google Scholar 

  8. Mortensen OV, Thomassen M, Larsen MB, Whittemore SR, Wiborg O (1999) Functional analysis of a novel human serotonin transporter gene promoter in immortalized raphe cell. Brain Res Mol Brain Res 68:141–148

    Article  PubMed  CAS  Google Scholar 

  9. Ogilvie AD, Battersby S, Bubb VJ, Fink G, Harmar AJ, Goodwim GM, Smith CA (1996) Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet 347:731–733

    Article  PubMed  CAS  Google Scholar 

  10. Mackenzie A, Quinn J (1999) A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo. Proc Natl Acad Sci USA 96:15251–15255

    Article  PubMed  CAS  Google Scholar 

  11. Hranilovic D, Stefulj J, Schwab S, Borrmann-Hassenbach M, Albus M, Jernej B, Wildenauer D (2004) Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression. Biol Psychiatry 55:1090–1094

    Article  PubMed  CAS  Google Scholar 

  12. Yeo A, Boyd P, Lumsden S, Saunders T, Handley A, Stubbins M, Knaggs A, Asquith S, Taylor I, Bahari B, Crocker N, Rallan R, Varsani S, Montgomery D, Alpers DH, Dukes GE, Purvis I, Hicks GA (2004) Association between a functional polymorphism in the serotonin transporter gene and diarrhea predominant irritable bowel syndrome in women. Gut 53:1452–1458

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Kim HJ, Camilleri M, Carlson PJ, Cremonini F, Ferber I, Stephens D, Mckinzie S, Zinsmeister AR, Urrutia R (2004) Association of distinct α2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders. Gut 53:829–837

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  16. Camilleri M, Atanasova E, Carlson PJ, Ahmad U, Kim HJ, Viramontes BE, Mckinzie S, Urrutia R (2002) Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology 123:425–432

    Article  PubMed  CAS  Google Scholar 

  17. Muller-Lissner SA, Fumagalli I, Bardhan KD, Pace F, Pecherr E, Nault B, Ruegg P (2001) Tegaserod, a 5-HT4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 15:1655–1666

    Article  PubMed  CAS  Google Scholar 

  18. Kellow J, Lee OY, Chang FY, Thongsawat S, Mazlam MZ, Yuen H, Gwee KA, Bak YT, Jones J, Wagner A (2003) An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Gut 52:671–676

    Article  PubMed  CAS  Google Scholar 

  19. Nyhlin H, Bang C, Elsborg L, Silvennoinen J, Holme I, Ruegg P, Jones J, Wagner A (2004) A double-blind, placebo-controlled, randomized study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Scand J Gastroenterol 39:119–126

    Article  PubMed  CAS  Google Scholar 

  20. Smeraldi E, Zanardi R, Benedetti F, Di Bella D, Perez J, Catalano M (1998) Polymorphism with the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol Psychiatry 3:508–511

    Article  PubMed  CAS  Google Scholar 

  21. Smits KM, Smits LJM, Schouten JSAG, Stelma FF, Nelemans P, Prins MH (2004) Influence of SERTPR and STin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic review. Mol Psychiatry 9:433–441

    Article  PubMed  CAS  Google Scholar 

  22. Muller-Lissner S, Koch G, Talley NJ, Drossman D, Rueegg P, Dunger-Baldauf C, Lefkowitz M (2003) Subject's global assessment of relief: an appropriate method to assess the impact of treatment on irritable bowel syndrome-related symptoms in clinical trials. J Clin Epidemiol 56:310–316

    Article  PubMed  Google Scholar 

  23. Gelernter J, Cubells JF, Kidd JR, Pakstis AJ, Kidd KK (1999) Population studies of polymorphisms of the Serotonin transporter protein gene. Am J Med Genet (Neuropsychiatr Genet) 88:61–66

    Article  CAS  Google Scholar 

  24. Tsai SJ, Ouyang WC, Hong CJ (2002) Association for serotonin transporter gene variable number tandem repeat polymorphism and schizophrenic disorders. Neuropsychobiology 45:131–133

    Article  PubMed  CAS  Google Scholar 

  25. Hoehe MR, Wendel B, Grunewald I, Chiaroni P, Levy N, Morris-Rosendahl D, Macher JP, Sander T, Crocq MA (1998) Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorder. Am J Med Genet 81:1–3

    Article  PubMed  CAS  Google Scholar 

  26. Gelernter J, Kranzler H, Cubells JF (1997) Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African and European and Japanese populations and alcohol–dependent subjects. Hum Genet 101:243–246

    Article  PubMed  CAS  Google Scholar 

  27. Kunugi H, Hattori M, Kato T, Tatsumi M, Sakai T, Sasaki T, Hirose T, Nanko S (1997) Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder. Mol Psychiatry 2:457–462

    Article  PubMed  CAS  Google Scholar 

  28. You JS, Hu SY, Chen BL, Zhang HG (2005) Serotonin transporter and tryptophan hydroxylase gene polymorphism in Chinese patients with generalized anxiety disorder. Psychiatr Genet 15:7–11

    Article  PubMed  Google Scholar 

  29. Wang BM, Wang YM, Zhang WM, Zhang QY, Liu WT, Jiang K, Zhang J (2004) Serotonin transporter gene polymorphism in irritable bowel syndrome. Zhonghua Nei Ke Za Zhi 43:439–441 (in Chinese)

    PubMed  CAS  Google Scholar 

  30. Serretti A, Benedetti F, Zanardi R, Smeraldi E (2005) The influence of serotonin transporter promoter polymorphism (SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatment. Prog Neuropsychopharmacol Biol Psychiatry 29:1074–1084

    Article  PubMed  CAS  Google Scholar 

  31. Liu MT, Rayport S, Jiang Y, Murphy DL, Gershon MD (2002) Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter. Am J Physiol Gastrointest 283:G1398–G1411

    CAS  Google Scholar 

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Correspondence to Yuqiang Nie.

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Li, Y., Nie, Y., Xie, J. et al. The Association of Serotonin Transporter Genetic Polymorphisms and Irritable Bowel Syndrome and Its Influence on Tegaserod Treatment in Chinese Patients. Dig Dis Sci 52, 2942–2949 (2007). https://doi.org/10.1007/s10620-006-9679-y

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  • DOI: https://doi.org/10.1007/s10620-006-9679-y

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