The development of functional gastrointestinal diseases: Genetic aspects


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Abstract

Motility disorders of the upper and lower gastrointestinal tract encompass a very wide range of structurally different diseases. Functional dyspepsia and irritable bowel syndrome (IBS) are the most common functional gastrointestinal disorders in clinical practice. In spite of the considerable prevalence of these functional diseases, the knowledge of their development mechanisms is very scarce. Recent investigations of the impact of the motor and sensory components of the pathogenesis of these diseases have demonstrated that the development of IBS is associated with serotonin transporter gene (5-HTTLPR) impairment and that the patients with IBS show the inadequate response to nonselective cannabinoid receptor agonists, which is caused by cannabinoid receptor gene (CNR1) polymorphism. Most investigations (mainly trials with small sample sizes) dealing with the identification of pharmacogenetic features have indicated that there is a preponderance of patients with intermediary metabolism among those with functional gastrointestinal diseases. However, larger investigations are necessary for a more exact understanding of this aspect.

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V A Akhmedov

References

  1. Brant SR. Promises, delivery, and challenges of inflammatory bowel disease risk gene discovery. Clin Gastroenterol Hepatol. 2013;11(1):22-26.
  2. Camilleri M. Genetics of human gastrointestinal sensation. Neurogastroenterol Motil. 2013;25(6) 458-466.
  3. 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.
  4. Lenbo T, Zaman MS, Chavez NF, Krueger R, Jones MP, Talley NJ. Concordance of IBS among monozygotic and dizygotic twins. Gastroenterol. 2001;120(Suppl 1):A-66.
  5. Fukudo S, Kanazawa M, Mizuno T, Hamaguchi T, Kano M, Watanabe S. Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention. Neuroimage. 2009;47:946-951. doi: 10.1016/j.neuroimage.2009.04.08319426812.
  6. Oshima T, Nakajima S, Yokoyama T, Toyoshima F, Sakurai J, Tanaka J, Tomita T, Kim Y, Hori K, Matsumoto T, Miwa H. The G-protein beta3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia. BMC Med Genet. 2010;11:13-16. doi: 10.1186/1471-2350-11-13.
  7. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, Fujita H, Yoshioka D, Arima Y, Okubo M, Hirata I, Nakano H. Genetic polymorphisms of molecules associated with inflammation and immune response in Japanese subjects with functional dyspepsia. Int J Mol Med. 2007;20:717-723.
  8. Tahara T, Shibata T, Wang F, Yamashita H, Hirata I, Arisawa T. Genetic Polymorphisms of Molecules Associated with Innate Immune Responses, TRL2 and MBL2 Genes in Japanese Subjects with Functional Dyspepsia. J Clin Biochem Nutr. 2010;47:217-223. doi: 10.3164/jcbn.10-40.
  9. Camilleri M, Busciglio I, Carlson P, McKinzie S, Burton D, Baxter K, Ryks M, Zinsmeister AR. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol Gastrointest LiverPhysiol. 2008;295:219-225. doi: 10.1152/ajpgi.90202.2008.
  10. Camilleri CE, Carlson PJ, Camilleri M, Castillo EJ, Locke GR 3rd, Geno DM, Stephens DA, Zinsmeister AR, Urrutia R. A study of candidate genotypes associated with dyspepsia in a U.S. community. Am J Gastroenterol. 2006;101:581-592.
  11. van Lelyveld N, Linde JT, Schipper M, Samsom M. Candidate genotypes associated with functional dyspepsia. Neurogastroenterol Motil. 2008;20:767-773. doi: 10.1111/j.1365-2982.2008.01102.x.
  12. Camilleri M, Kolar GJ, Vazquez-Roque MI, Carlson P, Burton DD, Zinsmeister AR. Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits. Am J Physiol GastrointestLiver Physiol. 2013;304:553-560. doi: 10.1152/ajpgi.00376.2012.
  13. Holtmann G, Siffert W, Haag S, Mueller N, Langkafel M, Senf W, Zotz R, Talley NJ. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971-979.
  14. Arisawa T, Tahara T, Shiroeda H, Minato T, Matsue Y, Saito T, Fukuyama T, Otsuka T, Fukumura A, Nakamura M, Shibata T. Genetic polymorphisms of SCN10A are associated with functional dyspepsia in Japanese subjects. JGastroenterol. 2013;48:73-80. doi: 10.1007/s00535-012-0602-3.
  15. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, Fujita H, Yoshioka D, Arima Y, Okubo M, Hirata I, Nakano H. Genetic polymorphisms of cyclooxygenase-1 (COX-1) are associated with functional dyspepsia in Japanese women. J Womens Health (Larchmt). 2008;17:1039-1043. doi: 10.1089/jwh.2007.0720.
  16. Camilleri M, Carlson P, Zinsmeister AR, McKinzie S, Busciglio I, Burton D, Zucchelli M, D’Amato M. Neuropeptide S receptor induces neuropeptide expression and associates with intermediate phenotypes of functional gastrointestinal disorders. Gastroenterology. 2010;138:98-107. doi: 10.1053/j.gastro.2009.08.051.
  17. van Kerkhoven LA, Laheij RJ, Jansen JB. Meta-analysis: a functional polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel syndrome. Aliment Pharmacol Ther. 2007;26:979-986.
  18. Sikander A, Rana SV, Sinha SK, Prasad KK, Arora SK, Sharma SK, Singh K. Serotonin transporter promoter variant: analysis in Indian IBS patients and control population. J Clin Gastroenterol. 2009;43:957-961. doi: 10.1097/mcg.0b013e3181b37e8c.
  19. Ghoshal UC, Abraham P, Bhatt C, Choudhuri G, Bhatia SJ, Shenoy KT, Banka NH, Bose K, Bohidar NP, Chakravartty K, Shekhar NC, Desai N, Dutta U, Das G, Dutta S, Dixit VK, Goswami BD, Jain RK, Jain S, Jayanthi V, Kochhar R, Kumar A, Makharia G, Mukewar SV, Mohan Prasad VG, Mohanty A, Mohan AT, Sathyaprakash BS, Prabhakar B, Philip M, Veerraju EP, Ray G, Rai RR, Seth AK, Sachdeva A, Singh SP, Sood A, Thomas V, Tiwari S, Tandan M, Upadhyay R, Vij JC. Epidemiological and clinical profile of irritable bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force. Indian. J Gastroenterol. 2008;27:22-28.
  20. Ford AC, Forman D, Bailey AG, Axon AT, Moayyedi P. Irritable bowel syndrome: a 10-year natural history of symptoms and factors that influence consultation behavior. Am J Gastroenterol. 2008;103:1229-1239. doi: 10.1111/j.1572-0241.2007.01740.x.
  21. Gulewitsch MD, Enck P, Hautzinger M, Schlarb AA. Irritable bowel syndrome symptoms among German students: prevalence, characteristics, and associations to somatic complaints, sleep, quality of life, and childhood abdominal pain. Eur J Gastroenterol Hepatol. 2011;23:311-316. doi: 10.1097/meg.0b013e3283457b1e.
  22. Niesler B, Kapeller J, Fell C, Atkinson W, Möller D, Fischer C, Whorwell P, Houghton LA. 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. doi: 10.1097/meg.0b013e32832e9d6b.
  23. Jarrett ME, Kohen R, Cain KC, Burr RL, Poppe A, Navaja GP, Heitkemper MM. Relationship of SERT polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome. Biol Res Nurs. 2007;9:161-169.
  24. Naliboff BD, Derbyshire SW, Munakata J, Berman S, Mandelkern M, Chang L, Mayer EA. Cerebral activation in patients with irritable bowel syndrome and control subjects during rectosigmoid stimulation. Psychosom Med. 2001;63:365-375.
  25. Liu J, Wei X, Zhao C, Hu S, Duan J, Ju G, Wong-Riley MT, Liu Y. 5-HT induces enhanced phrenic nerve activity via 5-HT2A receptor/PKC mechanism in anesthetized rats. Eur J Pharmacol. 2011;657:67-75. doi: 10.1016/j.ejphar.2011.01.048.
  26. Enoch MA, Goldman D, Barnett R, Sher L, Mazzanti CM, Rosenthal NE. Association between seasonal affective disorder and the 5-HT2A promoter polymorphism, –1438G/A. Mol Psychiatry. 1999;4:89-92.
  27. Nakamura T, Matsushita S, Nishiguchi N, Kimura M, Yoshino A, Higuchi S. Association of a polymorphism of the 5HT2A receptor gene promoter region with alcohol dependence. Mol Psychiatry. 1999;4:85-88.
  28. Pata C, Erdal E, Yazc K, Camdeviren H, Ozkaya M, Ulu O. Association of the –1438 G/A and 102 T/C polymorphism of the 5-HT2A receptor gene with irritable bowel syndrome 5-HT2A gene polymorphism in irritable bowel syndrome. J Clin Gastroenterol. 2004;38:561-566.
  29. Markoutsaki T, Karantanos T, Gazouli M, Anagnou NP, Karamanolis DG. HT2A receptor gene polymorphisms and irritable bowel syndrome. J Clin Gastroenterol. 2011;45:514-517. doi: 10.1097/mcg.0b013e318205e13b.
  30. Viramontes BE, Malcolm A, Camilleri M, Szarka LA, McKinzie S, Burton DD, Zinsmeister AR. Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans. Am JPhysiol Gastrointest Liver Physiol. 2001;281:1468-1476.
  31. Kim HJ, Camilleri M, Carlson PJ. Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders. Gut. 2004;53:829-837.
  32. Sikander A, Rana SV, Sharma SK, Sinha SK, Arora SK, Prasad KK, Singh K. Association of alpha 2A adrenergic receptor gene (ADRAlpha2A) polymorphism with irritable bowel syndrome, microscopic and ulcerative colitis. Clin Chim Acta. 2010;411:59-63. doi: 10.1016/j.cca.2009.10.003.
  33. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, Goldman D. COMT val158met genotype affects muopioid neurotransmitter responses to a pain stressor. Science. 2003;299:1240-1243.
  34. Park JM, Choi MG, Cho YK, Lee IS, Kim SW, Choi KY, Chung IS. Cannabinoid receptor 1 gene polymorphism and irritable bowel syndrome in the Korean population: a hypothesis-generating study. J ClinGastroenterol. 2011;45:45-49. doi: 10.1097/mcg.0b013e3181dd1573.
  35. Sato N, Suzuki N, Sasaki A, Aizawa E, Obayashi T, Kanazawa M, Mizuno T, Kano M, Aoki M, Fukudo S. Corticotropinreleasing hormone receptor 1 gene variants in irritable bowel syndrome. PLoS One. 2012;7:e42450. doi: 10.1371/journal.pone.0042450.
  36. Hua MC, Chao HC, Yao TC, Lai MW, Huang JL; PATCH Study Group. Investigation ofinterleukin-10 promoter polymorphisms and interleukin-10 levels in children with irritable bowel syndrome. Gut Liver. 2013;7:430-436. doi: 10.5009/gnl.2013.7.4.430.
  37. Bashashati M, Rezaei N, Bashashati H, Shafieyoun A, Daryani NE, Sharkey KA, Storr M. Cytokine gene polymorphisms are associated with irritable bowel syndrome: a systematic review and meta-analysis. Neurogastroenterol Motil. 2012;24:1102-1112. doi: 10.1111/j.1365-2982.2012.01990.x.
  38. Romero-Valdovinos M, Gudiño-Ramírez A, Reyes-Gordillo J. Interleukin-8 and -10 gene polymorphisms in irritable bowel syndrome. MolBiol Rep. 2012;39:8837-8843.
  39. Saito YA, Larson JJ, Atkinson EJ, Ryu E, Almazar AE, Petersen GlM, Talley NJ. The role of 5-HTT LPR and GNβ3 825C& gt; T polymorphisms and gene-environment interactions in irritable bowel syndrome (IBS). Dig Dis Sci. 2012;57:2650-2657. doi: 10.1007/s10620-012-2319-9.
  40. Shiotani A, Kusunoki H, Kimura Y, Ishii M, Imamura H, Tarumi K, Manabe N, Kamada T, Hata J, Haruma K. S100A expression and interleukin-10 polymorphisms are associated with ulcerative colitis and diarrhea predominant irritable bowel syndrome. Dig Dis Sci. 2013;58:2314-2323. doi: 10.1007/s10620-013-2677-y.
  41. Meaney MJ, Szyf M, Seckl JR. Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends. Mol Med. 2007;13:269-277.
  42. Zhang JP, Malhotra AK. Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction. Expert Opin Drug Metab Toxicol. 2011;7:9-37.
  43. Coutinho SV, Plotsky PM, Sablad M, Miller JC, Zhou H, Bayati AI, McRoberts JA, Mayer EA. Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol Gastrointest Liver Physiol. 2002;282:307-316.
  44. Dinan TG, Quigley EM, Ahmed SM, Scully P, O’Brien S, O’Mahony L, O’Mahony S, Shanahan F, Keeling PW. Hypothalamic—pituitary—gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology. 2006;130:304-311.
  45. Li Y, Nie Y, Xie J, Tang W, Liang P, Sha W, Yang H, Zhou Y. The association of serotonin transporter genetic polymorphisms and irritable bowel syndrome and its influence on tegaserod treatment in Chinese patients. Dig Dis Sci. 2000;52:2942-2949.
  46. Clarke G, Fitzgerald P, Cryan JF, Cassidy EM, Quigley EM, Dinan TG. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort. BMCGastroenterol. 2009;9:6-9. doi: 10.1186/1471-230x-9-6.
  47. Wong BS, Camilleri M, Carlson PJ, Odunsi-Shiyanbade S, McKinzie S, Busciglio I, Burton D, Zinsmeister AR. Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea. Dig Dis Sci. 2012;57(5):1222-1226. doi: 10.1007/s10620-012-2035-5.
  48. Wong BS, Camilleri M, Carlson PJ, Guicciardi ME, Burton D, McKinzie S, Rao AS, Zinsmeister AR, Gores GJ. A klothoβ variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea. Gastroenterology. 2011;140:1934-1942. doi: 10.1053/j.gastro.2011.02.063.
  49. Camilleri M1, Atanasova E, Carlson PJ, Ahmad U, Kim HJ, Viramontes BE, McKinzie S, Urrutia R. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2002;123:425-432.
  50. Givens RC, Watkins PB. Pharmacogenetics and clinical gastroenterology. Gastroenterology. 2003;125:240-248.
  51. Xie HG, Kim RB, Wood AJ, Stein CM. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol. 2001;41:815-850.
  52. Camilleri M, Carlson P, McKinzie S, Grudell A, Busciglio I, Burton D, Baxter K, Ryks M, Zinsmeister AR. Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation. Am J PhysiolGastrointest Liver Physiol. 2008;294:13-19.
  53. Clarke G, Quigley EM, Cryan JF, Dinan TG.Irritable bowel syndrome: towards biomarker identification. Trends Mol Med. 2009;15:478-489. doi: 10.1016/j.molmed.2009.08.001.
  54. Sistonen J, Fuselli S, Palo JU, Chauhan N, Padh H, Sajantila A. Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales. Pharmacogenet Genomics. 2009;19:170-179. doi: 10.1097/fpc.0b013e32831ebb30.

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