The role of pharmacogenetics in nonmalignant gastrointestinal diseases

Nature Reviews Gastroenterology and Hepatology

Volumn 9, Issue 3, 2012, Pages 173-184

  Camilleri, Michael ^a  

^a MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 MERCAPTOPURINE DERIVATIVE; ALOSETRON; AZATHIOPRINE; BILE ACID; CLOPIDOGREL; CORTICOSTEROID; CYCLOSPORIN A; CYTOCHROME P450; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DOMPERIDONE; GLYCOPROTEIN P; METHOTREXATE; METOCLOPRAMIDE; PLACEBO; PROTON PUMP INHIBITOR; SEROTONIN UPTAKE INHIBITOR; TACROLIMUS; TEGASEROD; TRICYCLIC ANTIDEPRESSANT AGENT; XANTHINE OXIDASE;

ADVERSE OUTCOME; CONSTIPATION; CROHN DISEASE; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG METABOLISM; DRUG THERAPY; DYSTONIC DISORDER; ENTERITIS; GASTROINTESTINAL DISEASE; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL MOTILITY DISORDER; GENE EXPRESSION PROFILING; GENETIC VARIABILITY; GENOTYPE; GRAPEFRUIT JUICE; HUMAN; HYPERSENSITIVITY; IRRITABLE COLON; NONHUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; PURINE METABOLISM; REFLUX ESOPHAGITIS; REVIEW; STOMACH PARESIS; ULCERATIVE COLITIS;

GASTROENTEROLOGY; GASTROINTESTINAL DISEASES; HUMANS; INDIVIDUALIZED MEDICINE; PHARMACOGENETICS;

EID: 84858081488     PISSN: 17595045     EISSN: 17595053     Source Type: Journal    
DOI: 10.1038/nrgastro.2012.2     Document Type: Review

References (132)

1. Camilleri, M. Scintigraphic biomarkers for colonic dysmotility. Clin. Pharmacol. Ther. 87, 748-753 (2010).
2. Givens, R. C. & Watkins, P. B. Pharmacogenetics and clinical gastroenterology. Gastroenterology 125, 240-248 (2003). (Pubitemid 36799124)
3. Wang, L., McLeod, H. L. & Weinshilboum, R. M. Genomics and drug response. N. Engl. J. Med. 364, 1144-1153 (2011).
4. Roden, D. M. et al. Pharmacogenomics: challenges and opportunities. Ann. Intern. Med. 21, 749-757 (2006). (Pubitemid 351650355)
5. Evans, W. E. & Relling, M. V. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286, 487-491 (1999).
6. Roden, D. M. & George, A. L. Jr. The genetic basis of variability in drug responses. Nat. Rev. Drug Disc. 1, 37-44 (2002). (Pubitemid 37361402)
7. Evans, W. E. & McLeod, H. L. Pharmacogenomics-drug disposition, drug targets, and side effects. N. Engl. J. Med. 348, 538-549 (2003). (Pubitemid 36159890)
8. Naranjo, C. A. et al. A method for estimating the probability of adverse drug reactions. Clin. Pharmacol. Ther. 30, 239-245 (1981). (Pubitemid 12149145)
9. Gardiner, S. J. & Begg, E. J. Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol. Rev. 58, 521-590 (2006). (Pubitemid 44403684)
10. Holtzman, C. W., Wiggins, B. S. & Spinler, S. A. Role of P?glycoprotein in statin drug interactions. Pharmacotherapy 26, 1601-1607 (2006). (Pubitemid 44704473)
11. Farrell, R. J. et al. High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy. Gastroenterology 118, 279-288 (2000). (Pubitemid 30067501)
12. Hirano, T. et al. MDR1 mRNA expressions in peripheral blood mononuclear cells of patients with ulcerative colitis in relation to glucocorticoid administration. J. Clin. Pharmacol. 44, 481-486 (2004). (Pubitemid 38509716)
13. Prandota, J. Advances of molecular clinical pharmacology in gastroenterology and hepatology. Am. J. Ther. 17, e137-e162 (2010).
14. Mendoza, J. L. et al. MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease. Inflamm. Bowel Dis. 13, 585-590 (2007). (Pubitemid 46799643)
15. Herrlinger, K. R. et al. ABCB1 single-nucleotide polymorphisms determine tacrolimus response in patients with ulcerative colitis. Clin. Pharmacol. Ther. 89, 422-428 (2011).
16. Daniel, F. et al. Multidrug resistance gene?1 polymorphisms and resistance to cyclosporine A in patients with steroid resistant ulcerative colitis. Inflamm. Bowel Dis. 13, 19-23 (2007). (Pubitemid 46080005)
17. Parkman, H. P. et al. Domperidone treatment for gastroparesis: demographic and pharmacogenetic characterization of clinical efficacy and side-effects. Dig. Dis. Sci. 56, 115-124 (2011).
18. Gow, J. M., Hodges, L. M., Chinn, L. W. & Kroetz, D. L. Substrate-dependent effects of human ABCB1 coding polymorphisms. J. Pharmacol. Exp. Ther. 325, 435-442 (2008). (Pubitemid 351574805)
19. Lewis, D. F. 57 varieties: the human cytochromes P450. Pharmacogenomics 5, 305-318 (2004). (Pubitemid 38499969)
20. Ingelman-Sundberg, M. Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn Schmiedebergs Arch. Pharmacol. 369, 89-104 (2004). (Pubitemid 38161226)
21. Sistonen, J. et al. Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales. Pharmacogenet. Genomics 19, 170-179 (2009).
22. Aklillu, E., Herrlin, K., Gustafsson, L. L., Bertilsson, L. & Ingelman-Sundberg, M. Evidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living in Ethiopia or in Sweden. Pharmacogenetics 12, 375-383 (2002). (Pubitemid 34816417)
23. Fuselli, S. et al. Evolution of detoxifying systems: the role of environment and population history in shaping genetic diversity at human CYP2D6 locus. Pharmacogenet. Genomics 20, 485-499 (2010).
24. Xie, H.?G., Kim, R. B., Wood, A. J. J. & Stein, C. M. Molecular basis of ethnic differences in drug disposition and response. Annu. Rev. Pharmacol. Toxicol. 41, 815-850 (2001). (Pubitemid 32385908)
25. Dalén, P., Dahl, M.?L., Bernal Ruiz, M. L., Nordin, J. & Bertilsson, L. 10-Hydroxylation of nortriptyline in Caucasians with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin. Pharmacol. Ther. 63, 444-452 (1998). (Pubitemid 28214968)
26. Aklillu, E. et al. Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP 2D6 alleles. J. Pharmacol. Exp. Ther. 278, 441-446 (1996). (Pubitemid 27167124)
27. Ford, A. C., Talley, N. J., Schoenfeld, P. S., Quigley, E. M. & Moayyedi, P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 58, 367-378 (2009).
28. Zhang, J. P. & Malhotra, A. K. Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction. Expert Opin. Drug Metab. Toxicol. 7, 9-37 (2011).
29. Caraco, Y., Sheller, J. & Wood, A. J. Pharmacogenetic determination of the effects of codeine and prediction of drug interactions. J. Pharmacol. Exp. Ther. 278, 1165-1174 (1996). (Pubitemid 27166966)
30. Gasche, Y. et al. Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N. Engl. J. Med. 351, 2827-2831 (2004). (Pubitemid 40051906)
31. Koren, G., Cairns, J., Chitayak, D., Gaedigk, A. & Leeder, S. J. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet 368, 704 (2006). (Pubitemid 44223697)
32. Madadi, P. et al. Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine. Can. Fam. Physician 53, 33-35 (2007). (Pubitemid 46166581)
33. De Morais, S. M. et al. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J. Biol. Chem. 269, 15419-15422 (1994).
34. De Morais, S. M. et al. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol. Pharmacol. 46, 594-598 (1994). (Pubitemid 24334747)
35. Ferguson, R. J. et al. A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S. mephenytoin. J. Pharmacol. Exp. Ther. 284, 356-361 (1998). (Pubitemid 28109566)
36. Ibeanu, G. C. et al. An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics 8, 129-135 (1998). (Pubitemid 28227321)
37. Xie, H.?G., Kim, R. B., Wood, A. J. J. & Stein, C. M. Molecular basis of ethnic differences in drug disposition and response. Annu. Rev. Pharmacol. Toxicol. 41, 815-850 (2001). (Pubitemid 32385908)
38. Klotz, U., Schwab, M. & Treiber, G. CYP2C19 polymorphism and PPIs. Basic Clin. Pharmacol. Toxicol. 95, 2-8 (2004).
39. Furuta, T. et al. Effect of cythochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin. Pharmacol. Ther. 72, 453-460 (2002). (Pubitemid 35178870)
40. Kawamura, M. et al. The effects of lansoprazole on erosive reflux oesophagitis are influenced by CYP2C19 polymorphism. Aliment. Pharmacol. Ther. 17, 965-973 (2003). (Pubitemid 36459609)
41. Chong, E. & Ensom, M. H. Pharmacogenetics of the PPIs: a systematic review. Pharmacotherapy 23, 460-471 (2003).
42. Schwab, M., Schaeffeler, E., Klotz, U. & Treiber, G. CYP2C19 polymorphism is a major predictor of treatment failure in white patients by use of lansoprazole-based quadruple therapy for eradication of Helicobacter pylori. Clin. Pharmacol. Ther. 76, 201-209 (2004). (Pubitemid 39221794)
43. de Leon, J., Susce, M. T. & Murray-Carmichael, E. The AmpliChip CYP450 genotyping test: Integrating a new clinical tool. Mol. Diagn. Ther. 10, 135-151 (2006). (Pubitemid 43974591)
44. Egan, L. J. et al. CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms. Aliment. Pharmacol. Ther. 17, 1521-1528 (2003). (Pubitemid 36831443)
45. Saitoh, T. et al. Influences of CYP2C19 polymorphism on recurrence of reflux esophagitis during PPI maintenance therapy. Hepatogastroenterology 56, 703-706 (2009).
46. Kita, T. et al. Different contribution of CYP2C19 in the in vitro metabolism of three PPIs. Biol. Pharm. Bull. 26, 386-390 (2003). (Pubitemid 39663632)
47. Ishizaki, T. & Horai, Y. Review article: cytochrome P450 and the metabolism of PPIs-emphasis on rabeprazole. Aliment. Pharmacol. Ther. 13 (SUPPL. 3), 27-36 (1999). (Pubitemid 29389409)
48. Fernando, H., Dart, A. M., Peter, K. & Shaw, J. A. Proton pump inhibitors, genetic polymorphisms and response to clopidogrel therapy. Thromb. Haemost. 105, 933-944 (2011).
49. Ellis, K. J., Stouffer, G. A., McLeod, H. L. & Lee, C. R. Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations. Pharmacogenomics 10, 1799-1817 (2009).
50. Chen, M., Wei, J. F., Xu, Y. N., Liu, X. J. & Huang, D. J. A meta-analysis of impact of PPIs on antiplatelet effect of clopidogrel. Cardiovasc. Ther. http://dx.doi.org/10.1111/j.1755-5922201100289.x.
51. Hsiao, F. Y. et al. Relationship between cardiovascular outcomes and PPI use in patients receiving dual antiplatelet therapy after acute coronary syndrome. Pharmacoepidemiol. Drug Saf. 20, 1043-1049 (2011).
52. Paré, G. et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N. Engl. J. Med. 363, 1704-1714 (2010).
53. Zabalza, M. et al. Meta-analyses of the association between cytochrome CYP2C19 loss- and gain?of?function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart http://dx.doi.org/10.1136/hrt.2011.227652.
54. Ma, T. K., Lam, Y. Y., Tan, V. P. & Yan, B. P. Variability in response to clopidogrel: how important are pharmacogenetics and drug interactions? Br. J. Clin. Pharmacol. 72, 697-706 (2011).
55. Giorgi, M. A., Cohen Arazi, H., Gonzalez, C. D. & Di Girolamo, G. Beyond efficacy: pharmacokinetic differences between clopidogrel, prasugrel and ticagrelor. Expert Opin. Pharmacother. 12, 1285-1295 (2011).
56. Michalets, E. L. & Williams, C. R. Drug interactions with cisapride: clinical implications. Clin. Pharmacokinet. 39, 49-75 (2000). (Pubitemid 30468204)
57. Rebbeck, T. R., Jaffe, J. M., Walker, A. H., Wein, A. J. & Malkowicz, S. B. Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J. Natl Cancer Inst. 90, 1225-1229 (1998). (Pubitemid 28407089)
58. Amirimani, B. et al. Increased transcriptional activity of the CYP3A4*1B promoter variant. Environ. Mol. Mutagen. 42, 299-305 (2003). (Pubitemid 38054375)
59. Hesselink, D. A. et al. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR?1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin. Pharmacol. Ther. 74, 245-254 (2003). (Pubitemid 37083100)
60. Hesselink, D. A. et al. Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR?1, CYP3A4, and CYP3A5 genes. Clin. Pharmacol. Ther. 76, 545-556 (2004). (Pubitemid 39601545)
61. Kane, G. C. & Lipsky, J. J. Drug-grapefruit juice interactions. Mayo Clin. Proc. 75, 933-942 (2000).
62. Kiani, J. & Imam, S. Z. Medicinal importance of grapefruit juice and its interaction with various drugs. Nutr. J. 6, 33 (2007).
63. Pierik, M. et al. Tumour necrosis factor receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab. Aliment. Pharmacol. Ther. 20, 303-310 (2004). (Pubitemid 39062133)
64. Dubinsky, M. C. et al. 6?MP metabolite profiles provide a biochemical explanation for 6?MP resistance in patients with inflammatory bowel disease. Gastroenterology 122, 904-915 (2002). (Pubitemid 34267273)
65. Grant, D. M., Tang, B. K. & Kalow, W. Variability in caffeine metabolism. Clin. Pharmacol. Ther. 33, 591-602 (1983). (Pubitemid 13098529)
66. Guerciolini, R., Szumlanski, C. & Weinshilboum, R. M. Human liver xanthine oxidase: nature and extent of individual variation. Clin. Pharmacol. Ther. 50, 663-672 (1991).
67. Saruwatari, J. et al. A population phenotyping study of three drug-metabolizing enzymes in Kyushu, Japan, with use of the caffeine test. Clin. Pharmacol. Ther. 72, 200-208 (2002). (Pubitemid 35034498)
68. Carrillo, J. A. & Benitez, J. Caffeine metabolism in a healthy Spanish population: N?acetylator phenotype and oxidation pathways. Clin. Pharmacol. Ther. 55, 293-304 (1994). (Pubitemid 24183729)
69. Kudo, M. et al. Functional characterization of human xanthine oxidase allelic variants. Pharmacogenet. Genomics 18, 243-251 (2008). (Pubitemid 351323239)
70. Kudo, M., Sasaki, T., Ishikawa, M., Hirasawa, N. & Hiratsuka, M. Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene. Drug Metab. Pharmacokinet. 25, 599-604 (2010).
71. Weinshilboum, R. M. Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug Metab. Dispos. 29, 601-605 (2001).
72. Yates, C. R. et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann. Intern. Med. 126, 608-614 (1997). (Pubitemid 27172187)
73. Weinshilboum, R. M. & Sladek, S. L. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am. J. Hum. Genet. 32, 651-662 (1980). (Pubitemid 10061685)
74. Lee, E. J. & Kalow, W. Thiopurine S-methyltransferase activity in a Chinese population. Clin. Pharmacol. Ther. 54, 28-33 (1993). (Pubitemid 23227513)
75. Cooper, S. C., Ford, L. T., Berg, J. D. & Lewis, M. J. Ethnic variation of thiopurine S-methyltransferase activity: a large, prospective population study. Pharmacogenomics 9, 303-309 (2008). (Pubitemid 351803933)
76. Moini, M. et al. The frequency and distribution of thiopurine S-methyltransferase alleles in south Iranian population. Mol. Biol. Rep. http://dx.doi.org/10.1007/s11033-011-1248-6.
77. Tumer, T. B. et al. The low frequency of defective TPMT alleles in Turkish population: a study on pediatric patients with acute lymphoblastic leukemia. Am. J. Hematol. 82, 906-910 (2007). (Pubitemid 47502696)
78. Hakooz, N. et al. Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population. Eur. J. Clin. Pharmacol. 66, 999-1003 (2010).
79. Cao, Q., Zhu, Q., Shang, Y., Gao, M. & Si, J. Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease. Digestion 79, 58-63 (2009). (Pubitemid 43780144)
80. Zhang, J. P., Zhou, S. F., Chen, X. & Huang, M. Determination of intra-ethnic differences in the polymorphisms of thiopurine S-methyltransferase in Chinese. Clin. Chim. Acta. 365, 337-341 (2006). (Pubitemid 43196457)
81. González-Del Angel, A. et al. Thiopurine S-methyltransferase (TPMT) genetic polymorphisms in Mexican newborns. J. Clin. Pharm. Ther. 34, 703-708 (2009).
82. Ronen, O., Cohen, S. B. & Rund, D. Evaluating frequencies of thiopurine S-methyl transferase (TPMT) variant alleles in Israeli ethnic subpopulations using DNA analysis. Isr. Med. Assoc. J. 12, 721-725 (2010).
83. Winter, J. et al. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease. Aliment. Pharmacol. Ther. 20, 593-599 (2004). (Pubitemid 39279046)
84. Colombel, J. F. et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 118, 1025-1030 (2000).
85. Lichtenstein, G. R., Abreu, M. T., Cohen, R. & Tremaine, W. American Gastroenterological Association Institute Medical Position Statement on cortocosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 130, 935-939 (2006). (Pubitemid 43374542)
86. Ansari, A. et al. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Aliment. Pharmacol. Ther. 16, 1743-1750 (2002).
87. Dubinsky, M. C. et al. Pharmacogenomics and metabolite measurement for 6?mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 118, 705-713 (2000). (Pubitemid 30171620)
88. Cuffari, C., Hunt, S. & Bayless, T. Utilisation of erythrocyte 6?thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease. Gut 48, 642-646 (2001). (Pubitemid 32378583)
89. Cuffari, C., Theoret, Y., Latour, S. & Seidman, E. G. 6?mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. Gut 39, 401-406 (1996). (Pubitemid 26338529)
90. Lamers, C. B. H. W., Griffioen, G., van Hogezand, R. A. & Veenendaal, R. A. Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease. Scand. J. Gastroenterol. 230, 111-115 (1999). (Pubitemid 29434519)
91. Ansari, A. et al. Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease. Aliment. Pharmacol. Ther. 28, 973-983 (2008).
92. Urano, W. et al. Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses. Pharmacogenetics 12, 183-190 (2002). (Pubitemid 34596782)
93. Guoqing, C. & Goeddel, D. V. TNF?R1 signaling: a beautiful pathway. Science 296, 1634-1635 (2002).
94. MacEwan, D. J. TNF receptor subtype signalling: differences and cellular consequences. Cell Signal. 14, 477-492 (2002). (Pubitemid 34230583)
95. Louis, E. et al. A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with ?308 TNF gene polymorphism. Scand. J. Gastroenterol. 37, 818-824 (2002). (Pubitemid 34836819)
96. Shetty, A. & Forbes, A. Pharmacogenomics of response to anti-tumor necrosis factor therapy in patients with Crohn's disease. Am. J. Pharmacogenomics 2, 215-221 (2002). (Pubitemid 35429311)
97. Mascheretti, S. et al. Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn's disease treated with infliximab. Pharmacogenomics J. 2, 127-136 (2002). (Pubitemid 34982216)
98. Mascheretti, S. et al. Response to infliximab treatment in Crohn's disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials. Pharmacogenetics 12, 509-515 (2002). (Pubitemid 35177080)
99. Vermeire, S. et al. NOD2/CARD15 does not influence response to infliximab in Crohn's disease. Gastroenterology 123, 106-111 (2002). (Pubitemid 34747530)
100. Louis, E. et al. Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease. Aliment. Pharmacol. Ther. 19, 511-519 (2004). (Pubitemid 38387177)
101. Louis, E. J. et al. Polymorphism in IgG Fc receptor gene FCGR3A and response to infliximab in Crohn's disease: a subanalysis of the ACCENT I study. Pharmacogenet. Genomics 16, 911-914 (2006). (Pubitemid 44772809)
102. Urcelay, E. et al. IBD5 polymorphisms in inflammatory bowel disease: association with response to infliximab. World J. Gastroenterol. 11, 1187-1192 (2005). (Pubitemid 40353007)
103. Vermeire, S., Van Assche, G. & Rutgeerts, P. Role of genetics in prediction of disease course and response to therapy. World J. Gastroenterol. 16, 2609-2615 (2010).
104. Gershon, M. D. Review article: serotonin receptors and transporters-roles in normal and abnormal gastrointestinal motility. Aliment. Pharmacol. Ther. 20 (SUPPL. 7), 3-14 (2004). (Pubitemid 39657670)
105. Lesch, K. P. et al. Organization of the human serotonin transporter gene. J. Neural Transm. Gen. Sect. 95, 157-162 (1994). (Pubitemid 2051960)
106. Murphy, D. L., Lerner, A., Rudnick, G. & Lesch, K. P. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol. Interv. 4, 109-123 (2004). (Pubitemid 38584973)
107. Lesch, K. P. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527-1531 (1996).
108. Chen, J. J. et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: abnormal intestinal motility and the expression of cation transporters. J. Neurosci. 21, 6348-6361 (2001). (Pubitemid 32737766)
109. Camilleri, M. et al. Candidate genes and sensory functions in health and irritable bowel syndrome. Am. J. Physiol. 295, G219-G225 (2008).
110. Coates, M. D. et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 126, 1657-1664 (2004). (Pubitemid 38736329)
111. Camilleri, M. et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology 132, 17-25 (2007). (Pubitemid 46108754)
112. Viramontes, B. E. et al. Gender-related differences in slowing colonic transit by a 5?HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome. Am. J. Gastroenterol. 96, 2671-2676 (2001).
113. Prather, C. M., Camilleri, M., Zinsmeister, A. R., McKinzie, S. & Thomforde, G. M. Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology 118, 463-468 (2000). (Pubitemid 30140843)
114. Kapeller, J. 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. 17, 2967-2977 (2008).
115. Camilleri, M. et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology 123, 425-432 (2002). (Pubitemid 34827186)
116. Li, Y. 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). (Pubitemid 47512533)
117. Wong, B. S. et al. A klotho? variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea. Gastroenterology 140, 1934-1942 (2011).
118. Rao, A. S. et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology 139, 1549-1558 (2010).
119. Wong, B. S. et al. Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea. Dig. Dis. Sci. (in press)
120. Shin, J. G., Soukhova, N. & Flockhart, D. A. Effect of antipsychotic drugs on human liver cytochrome P?450 (CYP) isoforms in vitro: preferential inhibition of CYP2D6. Drug Metab. Dispos. 27, 1078-1084 (1999). (Pubitemid 29409646)
121. van der Padt, A., van Schaik, R. H. & Sonneveld, P. Acute dystonic reaction to metoclopramide in patients carrying homozygous cytochrome P450 2D6 genetic polymorphisms. Neth. J. Med. 64, 160-162 (2006).
122. Lundstrom, K. & Turpin, M. P. Proposed schizophrenia-related gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest Virus System. Biochem. Biophys. Res. Commun. 225, 1068-1072 (1996). (Pubitemid 26319228)
123. Bakker, P. R., Van Harten, P. N. & Van Os, J. Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: a meta analysis. Schizophr. Res. 83, 185-192 (2006).
124. Li, Y. Y. et al. Serotonin transporter gene polymorphisms in irritable bowel syndrome and their impact on tegaserod treatment. Zhonghua Nei Ke Za Zhi. 45, 552-555 (2006).
125. FDA [online], http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ 2007/ucm108879.htm (2011).
126. Loughlin, J. et al. Tegaserod and the risk of cardiovascular ischemic events: an observational cohort study. J. Cardiovasc. Pharmacol. Ther. 15, 151-157 (2010).
127. Anderson, J. L. et al. Lack of association of tegaserod with adverse cardiovascular outcomes in a matched case-control study. J. Cardiovasc. Pharmacol. Ther. 14, 170-175 (2009).
128. Higgins, D. L. et al. The inability of tegaserod to affect platelet aggregation and coronary artery tone at supratherapeutic concentrations. Naunyn Schmiedebergs Arch. Pharmacol. http://dx.doi.org/10.1007/s00210-011-0687-x.
129. Relling, M. V. & Klein, T. E. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin. Pharmacol. Ther. 89, 464-467 (2011).
130. Teutsch, S. M. et al. The evaluation of genomic applications in practice and prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genet. Med. 11, 3-14 (2009).
131. Beitelshees, A. L. & Veenstra, D. L. Evolving research and stakeholder perspectives on pharmacogenomics. JAMA 306, 1252-1253 (2011).
132. Altman, R. B. Pharmacogenomics: "noninferiority" is sufficient for initial implementation. Clin. Pharmacol. Ther. 89, 348-350 (2011).