56
Views
0
CrossRef citations to date
0
Altmetric
Review

Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism

&
Pages 319-332 | Received 28 Nov 2023, Accepted 26 Apr 2024, Published online: 26 May 2024

References

  • Camilleri M, Chedid V. Leading article: actionable biomarkers: the key to resolving disorders of gastrointestinal function. Gut. 2020;69(10):1730–1737. doi: 10.1136/gutjnl-2019-320325
  • Camilleri M, BouSaba J. Potential value of biomarker-based approaches for evaluation and management of costly functional gastrointestinal diseases. Clin Gastroenterol Hepatol. 2023;21(10):2462–2472. doi: 10.1016/j.cgh.2023.04.030
  • Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372(9):793–795.
  • Eugene AR. Optimizing drug selection in psychopharmacology based on 40 significant CYP2C19- and CYP2D6-biased adverse drug reactions of selective serotonin reuptake inhibitors. Peer J. 2019 Oct 9;7:e7860. eCollection 2019. doi: 10.7717/peerj.7860
  • Keefer L, Ballou SK, Drossman DA, et al. A rome working team report on brain-gut behavior therapies for disorders of gut-brain interaction. Gastroenterology. 2022;162(1):300–315. doi: 10.1053/j.gastro.2021.09.015
  • Moshiree B, Drossman D, Shaukat A. AGA clinical practice update on evaluation and management of belching, abdominal bloating, and distention: expert review. Gastroenterology. 2023;165(3):791–800.e3. doi: 10.1053/j.gastro.2023.04.039
  • Camilleri M. Implications of pharmacogenomics to the management of IBS. Clin Gastroenterol Hepatol. 2019;17(4):584–594. doi: 10.1016/j.cgh.2018.04.052
  • Bielinski SJ, Olson JE, Pathak J, et al. Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time—using genomic data to individualize treatment protocol. Mayo Clin Proc. 2014;89(1):25–33. doi: 10.1016/j.mayocp.2013.10.021
  • Camilleri M. The role of pharmacogenetics in nonmalignant gastrointestinal diseases. Nat Rev Gastroenterol Hepatol. 2012;9(3):173–184. doi: 10.1038/nrgastro.2012.2
  • Pentikis HS, Connolly M, Trapnell CB, et al. The effect of multiple-dose, oral rifaximin on the pharmacokinetics of intravenous and oral midazolam in healthy volunteers. Pharmacotherapy. 2007;27(10):1361–1369. doi: 10.1592/phco.27.10.1361
  • Wang Z, Lin YS, Zheng XE, et al. An inducible cytochrome P450 3A4-dependent vitamin D catabolic pathway. Mol Pharmacol. 2012;81(4):498–509. doi: 10.1124/mol.111.076356
  • Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127–134. doi: 10.1002/cpt.147
  • Camilleri M, Katzka DA. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;302(10):G1075–84.
  • Camilleri M. Genetics of human gastrointestinal sensation. Neurogastroenterol Motil. 2013;25(6):458–466. doi: 10.1111/nmo.12132
  • Rao A, Wong B, Camilleri M, et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010;139(5):1549. doi: 10.1053/j.gastro.2010.07.052
  • Wong BS, Camilleri M, Carlson PJ, et al. 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
  • Wong BS, Camilleri M, Eckert D, et al. Randomized pharmacodynamic and pharmacogenetic trial of dronabinol effects on colon transit in irritable bowel syndrome-diarrhea. Neurogastroenterol Motil. 2012;24(4):358–65.e169. doi: 10.1111/j.1365-2982.2011.01874.x
  • 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(5292):1527–1531. doi: 10.1126/science.274.5292.1527
  • Fukudo S, Kanazawa M, Mizuno T, et al. Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention. Neuroimage. 2009;47(3):946–951. doi: 10.1016/j.neuroimage.2009.04.083
  • Camilleri M, Atanasova E, Carlson PJ, et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2002;123(2):425–432. doi: 10.1053/gast.2002.34780
  • 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. 2007;52(11):2942–2949. doi: 10.1007/s10620-006-9679-y
  • Zhang ZF, Duan ZJ, Wang LX, et al. The serotonin transporter gene polymorphism (5-HTTLPR) and irritable bowel syndrome: a meta-analysis of 25 studies. BMC Gastroenterol. 2014;14(1):23. doi: 10.1186/1471-230X-14-23
  • Colucci R, Gambaccini D, Ghisu N, et al. Influence of the serotonin transporter 5HTTLPR polymorphism on symptom severity in irritable bowel syndrome. PLOS ONE. 2013;8(2):e54831. doi: 10.1371/journal.pone.0054831
  • Jun S, Kohen R, Cain KC, et al. Associations of tryptophan hydroxylase gene polymorphisms with irritable bowel syndrome. Neurogastroenterol Motil. 2011;23(3):233–e116. doi: 10.1111/j.1365-2982.2010.01623.x
  • Shiotani A, Kusunoki H, Ishii M, et al. Pilot study of biomarkers for predicting effectiveness of ramosetron in diarrhea-predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPH1. Neurogastroenterol Motil. 2015;27(1):82–91. doi: 10.1111/nmo.12473
  • Kapeller J, Houghton LA, Monnikes H, et al. First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome. Hum Mol Genet. 2008;17(19):2967–2977. doi: 10.1093/hmg/ddn195
  • Kilpatrick LA, Labus JS, Coveleskie K, et al. The HTR3A polymorphism c. -42C > T is associated with amygdala responsiveness in patients with irritable bowel syndrome. Gastroenterology. 2011;140:1943–1951. doi: 10.1053/j.gastro.2011.03.011
  • Hammer C, Kapeller J, Endele M, et al. Functional variants of the serotonin receptor type 3A and B gene are associated with eating disorders. Pharmacogenet Genomics. 2009;19(10):790–799. doi: 10.1097/FPC.0b013e32833132b3
  • Yamada K, Hattori E, Iwayama Y, et al. Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression. Biol Psychiatry. 2006;60(2):192–201. doi: 10.1016/j.biopsych.2005.11.008
  • Berens S, Dong Y, Fritz N, et al. Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: a multicenter retrospective study. World J Gastroenterol. 2022;28(21):2334–2349. doi: 10.3748/wjg.v28.i21.2334
  • Kapeller J, Moller D, Lasitschka F, et al. Serotonin receptor diversity in the human colon: expression of serotonin type 3 receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E. J Comp Neurol. 2011;519(3):420–432. doi: 10.1002/cne.22525
  • Gu QY, Zhang J, Feng YC, et al. Association of genetic polymorphisms in HTR3A and HTR3E with diarrhea predominant irritable bowel syndrome. Int J Clin Exp Med. 2015;8(3):4581–4585.
  • Zhang Y, Huang Y, Bo P. Association between diarrhea-predominant irritable bowel syndrome and HTR3A, HTR3E gene polymorphism in Yangzhou,Jiangsu province, China. Zhonghua Liu Xing Bing Xue Za Zhi. 2013;34(7):721–724.
  • Zhang Y, Li Y, Hao Z, et al. Association of the serotonin receptor 3E Gene as a functional variant in the MicroRNA-510 target site with diarrhea predominant irritable bowel syndrome in Chinese women. J Neurogastroenterol Motil. 2016;22(2):272–281. doi: 10.5056/jnm15138
  • Camilleri M, Carlson P, BouSaba J, et al. Comparison of biochemical, microbial, and mucosal mRNA expression in bile acid diarrhea and irritable bowel syndrome-diarrhea. Gut. 2023;72(1):54–65. doi: 10.1136/gutjnl-2022-327471
  • Wong B, Camilleri M, Carlson P, et al. A Klothoβ variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea. Gastroenterology. 2011;140(7):1934–1942. doi: 10.1053/j.gastro.2011.02.063
  • Camilleri M, Shin A, Busciglio I, et al. Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion. Am J Physiol Gastrointest Liver Physiol. 2014;307(5):G508–16. doi: 10.1152/ajpgi.00178.2014
  • Camilleri M, Kolar GJ, Vazquez-Roque MI, et al. Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits. Am J Physiol Gastrointest Liver Physiol. 2013;304(5):G553–60. doi: 10.1152/ajpgi.00376.2012
  • Camilleri M, Carlson P, McKinzie S, et al. Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G13–9. doi: 10.1152/ajpgi.00371.2007
  • Celli J, Rappold G, Niesler B. The human serotonin type 3 receptor gene (HTR3A-E) allelic variant database. Human Mutation. 2017;38(2):137–147. doi: 10.1002/humu.23136
  • Kalantar JS, GR L 3rd, Zinsmeister AR, et al. Familial aggregation of irritable bowel syndrome: a prospective study. Gut. 2003;52(12):1703–1707. doi: 10.1136/gut.52.12.1703
  • Saito YA, Zimmerman JM, Harmsen WS, et al. Irritable bowel syndrome aggregates strongly in families: a family-based case control study. Neurogastroenterol Motil. 2008;20(7):790–797. doi: 10.1111/j.1365-2982.2007.01077.x
  • Bengtson MB, Ronning T, Vatn MH, et al. Irritable bowel syndrome in twins: genes and environment. Gut. 2006;55(12):1754–1759. doi: 10.1136/gut.2006.097287
  • Levy RL, Jones KR, Whitehead WE, et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology. 2001;121(4):799–804. doi: 10.1053/gast.2001.27995
  • Mohammed I, Cherkas LF, Riley SA, et al. Genetic influences in irritable bowel syndrome: a twin study. Am J Gastroenterol. 2005;100(6):1340–1344. doi: 10.1111/j.1572-0241.2005.41700.x
  • Morris-Yates A, Talley NJ, Boyce PM, et al. Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol. 1998;93(8):1311–1317. doi: 10.1111/j.1572-0241.1998.440_j.x
  • Zucchelli M, Camilleri M, Andreasson AN, et al. Association of TNFSF15 polymorphism with irritable bowel syndrome. Gut. 2011;60(12):1671–1677. doi: 10.1136/gut.2011.241877
  • Camilleri M, Carlson P, McKinzie S, et al. Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders: preliminary analysis. Neurogastroenterol Motil. 2011;23(10):935–e398. doi: 10.1111/j.1365-2982.2011.01749.x
  • Swan C, Duroudier NP, Campbell E, et al. Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα. Gut. 2013;62(7):985–994. doi: 10.1136/gutjnl-2011-301213
  • Wouters MM, Lambrechts D, Knapp M, et al. Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome. Gut. 2014;63(7):1103–1111. doi: 10.1136/gutjnl-2013-304570
  • Czogalla B, Schmitteckert A, Houghton LA, et al. A meta-analysis of immunogenetic case–control association studies in irritable bowel syndrome. Neurogastroenterol Motil. 2015;27(5):717–727. doi: 10.1111/nmo.12548
  • Ek WE, Reznichenko A, Ripke S, et al. Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts. Gut. 2015;64(11):1774–1782. doi: 10.1136/gutjnl-2014-307997
  • Bonfiglio F, Liu X, Smillie C, et al. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome. Cell Genom. 2021 Dec 8;1(3):None. doi: 10.1016/j.xgen.2021.100069
  • Drokhlyansky E, Smillie CS, Van Wittenberghe N, et al. The human and mouse enteric nervous system at single-cell resolution. Cell. 2020;182(6):1606–22.e23. doi: 10.1016/j.cell.2020.08.003
  • Montaño JA, Calavia MG, García-Suárez O, et al. The expression of ENa(+)C and ASIC2 proteins in pacinian corpuscles is differently regulated by TrkB and its ligands BDNF and NT-4. Neurosci Lett. 2009;463(2):114–118. doi: 10.1016/j.neulet.2009.07.073
  • Grider JR, Piland BE, Gulick MA, et al. Brain-derived neurotrophic factor augments peristalsis by augmenting 5-HT and calcitonin gene-related peptide release. Gastroenterology. 2006;130(3):771–780. doi: 10.1053/j.gastro.2005.12.026
  • Chen F, Yu Y, Wang P, et al. Brain-derived neurotrophic factor accelerates gut motility in slow-transit constipation. Acta Physiol (Oxf). 2014;212(3):226–238. doi: 10.1111/apha.12374
  • Coulie B, Szarka LA, Camilleri M, et al. Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans. Gastroenterology. 2000;119(1):41–50. doi: 10.1053/gast.2000.8553
  • Cottrell GS, Roosterman D, Marvizon JC, et al. Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. J Comp Neurol. 2005;490(3):239–255. doi: 10.1002/cne.20669
  • Cottrell GS, Alemi F, Kirkland JG, et al. Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract. Peptides. 2012;35(2):202–211. doi: 10.1016/j.peptides.2012.03.020
  • Sternini C. Enteric and visceral afferent CGRP neurons. Targets of innervation and differential expression patterns. Ann N Y Acad Sci. 1992;657(1):170–186. doi: 10.1111/j.1749-6632.1992.tb22766.x
  • Esfandyari T, Macnaughton WK, Quirion R, et al. A novel receptor for calcitonin gene-related peptide (CGRP) mediates secretion in the rat colon: implications for secretory function in colitis. FASEB J Off Publ Fed Am Soc Exp Biol. 2000;14(10):1439–1446. doi: 10.1096/fj.14.10.1439
  • Cox HM, Ferrar JA, Cuthbert AW. Effects of α- and β-calcitonin gene-related peptides upon ion transport in rat descending colon. Br J Pharmacol. 1989;97(4):996–998. doi: 10.1111/j.1476-5381.1989.tb12553.x
  • Tanaka Y, Kanazawa M, Kano M, et al. Relationship between sympathoadrenal and pituitary-adrenal response during colorectal distention in the presence of corticotropin-releasing hormone in patients with irritable bowel syndrome and healthy controls. PLOS ONE. 2018;13(7):e0199698. doi: 10.1371/journal.pone.0199698
  • Camilleri M, Zhernakova A, Bozzarelli I, et al. Genetics of irritable bowel syndrome: shifting gear via biobank-scale studies. Nat Rev Gastroenterol Hepatol. 2022;19(11):689–702. doi: 10.1038/s41575-022-00662-2
  • Dema A, Faust D, Lazarow K, et al. Cyclin-dependent kinase 18 controls trafficking of aquaporin-2 and its abundance through ubiquitin ligase STUB1, which functions as an AKAP. Cells. 2020;9(3):673. doi: 10.3390/cells9030673
  • De Oliveira Pepino R, Coelho F, Aparecida Buzanello Janku T, et al. Overview of PCTK3/CDK18: a cyclin-dependent kinase involved in specific functions in post-mitotic cells. Curr Med Chem. 2021;28(33):6846–6865. doi: 10.2174/0929867328666210329122147
  • Jin S, Xu Y, Zang H, et al. Expression of genes related to lipid transport in meat-type ducks divergent for low or high residual feed intake. Asian-Australas J Anim Sci. 2020;33(3):416–423. doi: 10.5713/ajas.19.0284
  • Keck S, Galati-Fournier V, Kym U, et al. Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease. Cell Mol Gastroenterol Hepatol. 2021;12(2):507–545. doi: 10.1016/j.jcmgh.2021.03.004
  • Schafmayer C, Harrison JW, Buch S, et al. Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms. Gut. 2019;68(5):854–865. doi: 10.1136/gutjnl-2018-317619
  • Linsalata M, Prospero L, Riezzo G, et al. Somatization is associated with altered serum levels of vitamin D, serotonin, and brain-derived neurotrophic factor in patients with predominant diarrhea irritable bowel syndrome. Neutogastroenterol Motil. 2023;35(3):e14512. doi: 10.1111/nmo.14512
  • Chang W-Y, Yang Y-T, She M-P, et al. 5-HT7 receptor-dependent intestinal neurite outgrowth contributes to visceral hypersensitivity in irritable bowel syndrome. Lab Invest. 2022;102(9):1023–1037. doi: 10.1038/s41374-022-00800-z
  • Vodicka M, Ergang P, Hrncir T, et al. Microbiota affects the expression of genes involved in HPA axis regulation and local metabolism of glucocorticoids in chronic psychosocial stress. Brain Behav Immun. 2018;73:615–624. doi: 10.1016/j.bbi.2018.07.007
  • Fukudo S. Role of corticotropin-releasing hormone in irritable bowel syndrome and intestinal inflammation. J Gastroenterol. 2007;42(Suppl 17):48–51. doi: 10.1007/s00535-006-1942-7
  • Kasubuchi M, Hasegawa S, Hiramatsu T, et al. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015;7(4):2839–2849. doi: 10.3390/nu7042839
  • Eijsbouts C, Zheng T, Kennedy NA, et al. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nat Genet. 2021;53(11):1543–1552. doi: 10.1038/s41588-021-00950-8
  • Wu Y, Murray GK, Byrne EM, et al. GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression. Nat Commun. 2021;12(1):1146. doi: 10.1038/s41467-021-21280-7
  • Gong W, Guo P, Li Y, et al. Role of the gut-brain axis in the shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders: a genome-wide pleiotropic analysis. JAMA Psychiatry. 2023;80(4):360–370. doi: 10.1001/jamapsychiatry.2022.4974
  • Nagel M, Watanabe K, Stringer S, et al. Item-level analyses reveal genetic heterogeneity in neuroticism. Nat Commun. 2018;9(1):905. doi: 10.1038/s41467-018-03242-8
  • Bock HH, Herz J. Reelin activates SRC family tyrosine kinases in neurons. Curr Biol. 2003;13(1):18–26. doi: 10.1016/S0960-9822(02)01403-3
  • Kim H-J, Hur SW, Park JB, et al. Histone demethylase PHF2 activates CREB and promotes memory consolidation. EMBO Rep. 2019;20(9):e45907. doi: 10.15252/embr.201845907
  • Detera-Wadleigh SD, Liu C-Y, Maheshwari M, et al. Sequence variation in DOCK9 and heterogeneity in bipolar disorder. Psychiatr Genet. 2007;17(5):274–286. doi: 10.1097/YPG.0b013e328133f352
  • Soufi-Afshar I, Moghadamnia A, Bijani A, et al. Comparison of pyridostigmine and bisacodyl in the treatment of refractory chronic constipation. Caspian J Intern Med. 2016 Winter;7(1):19–24.
  • Manini ML, Camilleri M, Grothe R, et al. Application of pyridostigmine in pediatric gastrointestinal motility disorders: a case series. Paediatr Drugs. 2018;20(2):173–180. doi: 10.1007/s40272-017-0277-6
  • Dinan TG, Clarke G, Quigley EM, et al. Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors. Am J Gastroenterol. 2008;103(10):2570–2576. doi: 10.1111/j.1572-0241.2008.01871.x
  • Parkman HP, Rao SS, Reynolds JC, et al. Functional constipation study investigators. Neurotrophin-3 improves functional constipation. Am J Gastroenterol. 2003;98(6):1338–1347. doi: 10.1111/j.1572-0241.2003.t01-1-07477.x
  • Mahurkar-Joshi S, Chang L. Epigenetic mechanisms in irritable bowel syndrome. Front Psychiatry. 2020;11:805. doi: 10.3389/fpsyt.2020.00805
  • Bradford K, Shih W, Videlock EJ, et al. Association between early adverse life events and irritable bowel syndrome. Clin Gastroenterol Hepatol. 2012;10(4):385–390.e3. doi: 10.1016/j.cgh.2011.12.018
  • Park SH, Videlock EJ, Shih W, et al. Adverse childhood experiences are associated with irritable bowel syndrome and gastrointestinal symptom severity. Neurogastroenterol Motil. 2016;28(8):1252–1260. doi: 10.1111/nmo.12826
  • Parker CH, Naliboff BD, Shih W, et al. Negative events during adulthood are associated with symptom severity and altered stress response in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2019;17(11):2245–2252. doi: 10.1016/j.cgh.2018.12.029
  • Meaney MJ, Szyf M. Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues Clin Neurosci. 2005;7(2):103–123. doi: 10.31887/DCNS.2005.7.2/mmeaney
  • Dothel G, Barbaro MR, Di Vito A, et al. New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics. J Gastroenterol. 2023;58(7):605–621. doi: 10.1007/s00535-023-01997-6
  • Paul B, Barnes S, Demark-Wahnefried W, et al. Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases. Clin Epigenet. 2015;7(1):112. doi: 10.1186/s13148-015-0144-7
  • Liu S, da Cunha AP, Rezende RMM, et al. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe. 2016;19(1):32–43. doi: 10.1016/j.chom.2015.12.005
  • Smith DA, Sadler MC, Altman RB. Promises and challenges in pharmacoepigenetics. Camb Prism Precis Med. 2023 Feb 9;1:e18. doi: 10.1017/pcm.2023.6
  • Kacevska M, Ivanov M, Ingelman-Sundberg M. Perspectives on epigenetics and its relevance to adverse drug reactions. Clin Pharmacol Ther. 2011;89(6):902–907. doi: 10.1038/clpt.2011.21
  • Banerjee M. Pharmacoepigenomics: a key determinant in resolving epigenomic parameters in pathogenesis and treatment response in complex diseases. Pharmacogenomics. 2022;23(2):81–84. doi: 10.2217/pgs-2021-0140
  • Swathy B, Saradalekshmi KR, Nair IV, et al. Pharmacoepigenomic responses of antipsychotic drugs on pharmacogenes are likely to be modulated by miRnas. Epigenomics. 2017;9:811–821. doi: 10.2217/epi-2016-0181
  • Jin J, Zhong XB. Epigenetic mechanisms contribute to intraindividual variations of drug metabolism mediated by cytochrome P450 enzymes. Drug Metab Dispos. 2023;51(6):672–684. doi: 10.1124/dmd.122.001007
  • Powell TR, Smith RG, Hackinger S, et al. DNA methylation in interleukin-11 predicts clinical response to antidepressants in GENDEP. Transl Psychiatry. 2013;3(9):e300. doi: 10.1038/tp.2013.73
  • Radosavljevic M, Svob Strac D, Jancic J, et al. The role of pharmacogenetics in personalizing the antidepressant and anxiolytic therapy. Genes (Basel). 2023;14(5):1095. doi: 10.3390/genes14051095
  • Hong S, Zheng G, Wiley JW. Epigenetic regulation of genes that modulate chronic stress-induced visceral pain in the peripheral nervous system. Gastroenterology. 2015;148(1):148–157.e7. doi: 10.1053/j.gastro.2014.09.032
  • Wiley JW, Zong Y, Zheng G, et al. Histone H3K9 methylation regulates chronic stress and IL-6–induced colon epithelial permeability and visceral pain. Neurogastroenterol Motil. 2020;32(12):e13941. doi: 10.1111/nmo.13941
  • Zheng L, Kelly CJ, Battista KD, et al. Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor-dependent repression of claudin-2. J Immunol. 2017;199:2976–2984. doi: 10.4049/jimmunol.1700105
  • Zhou Q, Yang L, Larson S, et al. Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1. Gut. 2016;65(5):797–805. doi: 10.1136/gutjnl-2013-306464
  • Martı´nez C, Rodino˜-Janeiro BK, Lobo B, et al. miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea. Gut. 2017;66(9):1537.1–1538. doi: 10.1136/gutjnl-2016-311477
  • Venkova K, Johnson AC, Myers B, et al. Exposure of the amygdala to elevated levels of corticosterone alters colonic motility in response to acute psychological stress. Neuropharmacology. 2010;58(7):1161–1167. doi: 10.1016/j.neuropharm.2010.02.012
  • Greenwood-Van Meerveld B, Moloney RD, Johnson AC, et al. Mechanisms of stress-induced visceral pain: implications in irritable bowel syndrome. J Neuroendocrinol. 2016 Aug;28(8). doi: 10.1111/jne.12361
  • Taché Y, Million M. Role of corticotropin-releasing factor signaling in stress-related alterations of colonic motility and Hyperalgesia. J Neurogastroenterol Motil. 2015;21(1):008–024. doi: 10.5056/jnm14162
  • Larauche M, Moussaoui N, Biraud M, et al. Brain corticotropin-releasing factor signaling: involvement in acute stress induced visceral analgesia in male rats. Neurogastroenterol Motil. 2019;31(2):e13489. doi: 10.1111/nmo.13489
  • Lennon EM, Maharshak N, Elloumi H, et al. Early life stress triggers persistent colonic barrier dysfunction and exacerbates colitis in adult IL-10−/− mice. Inflammation Bowel Dis. 2013;19(4):712–719. doi: 10.1097/MIB.0b013e3182802a4e
  • Santos J, Benjamin M, Yang PC, et al. Chronic stress impairs rat growth and jejunal epithelial barrier function: role of mast cells. Am J Physiol Gastrointest Liver Physiol. 2000;278(6):G847–54. doi: 10.1152/ajpgi.2000.278.6.G847
  • Castagliuolo I, Lamont JT, Qiu B, et al. Acute stress causes mucin release from rat colon: role of corticotropin releasing factor and mast cells. Am J Physiol. 1996;271(5):G884–92. doi: 10.1152/ajpgi.1996.271.5.G884
  • Moloney RD, Stilling RM, Dinan TG, et al. Early-life stress-induced visceral hypersensitivity and anxiety behavior is reversed by histone deacetylase inhibition. Neurogastroenterol Motil. 2015;27(12):1831–1836. doi: 10.1111/nmo.12675
  • Moloney RD, Johnson AC, O’Mahony SM, et al. Stress and the microbiota–gut–brain axis in visceral pain: relevance to irritable bowel syndrome. CNS Neurosci Ther. 2016;22(2):102–117. doi: 10.1111/cns.12490
  • Aguirre JE, Winston JH, Sarna SK. Neonatal immune challenge followed by adult immune challenge induces epigenetic-susceptibility to aggravated visceral hypersensitivity. Neurogastroenterol Motil. 2017;29(9):125. doi: 10.1111/nmo.13081
  • Li Q, Winston JH, Sarna SK. Developmental origins of colon smooth muscle dysfunction in IBS-like rats. Am J Physiol Gastrointest Liver Physiol. 2013;305(7):G503–12. doi: 10.1152/ajpgi.00160.2013
  • Mahurkar S, Polytarchou C, Iliopoulos D, et al. Genome-wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome. Neurogastroenterol Motil. 2016;28(3):410–422. doi: 10.1111/nmo.12741
  • Welgan P, Meshkinpour H, Beeler M. Effect of anger on colon motor and myoelectric activity in irritable bowel syndrome. Gastroenterology. 1988;94(5):1150–1156. doi: 10.1016/0016-5085(88)90006-6
  • Posserud I, Agerforz P, Ekman R, et al. Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress. Gut. 2004;53(8):1102–1108. doi: 10.1136/gut.2003.017962
  • Dickhaus B, Mayer EA, Firooz N, et al. Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress. Am J Gastroenterol. 2003;98(1):135–143. doi: 10.1111/j.1572-0241.2003.07156.x
  • Videlock EJ, Shih W, Adeyemo M, et al. The effect of sex and irritable bowel syndrome on HPA axis response and peripheral glucocorticoid receptor expression. Psychoneuroendocrinology. 2016;69:67–76. doi: 10.1016/j.psyneuen.2016.03.016
  • Drossman DA, Tack J, Ford AC, et al. Neuromodulators for functional gastrointestinal disorders (disorders of Gut−Brain interaction): a Rome foundation working team report. Gastroenterology. 2018;154(4):1140–1171.e1. doi: 10.1053/j.gastro.2017.11.279
  • Blagec K, Swen JJ, Koopmann R, et al. Pharmacogenomics decision support in the U-PGx project: results and advice from clinical implementation across seven European countries. PLOS ONE. 2022;17(6):e0268534. doi: 10.1371/journal.pone.0268534

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.