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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (2) : 180-190     DOI: 10.1007/s11684-013-0249-3
Pharmacogenomics can improve antipsychotic treatment in schizophrenia
Qingqing Xu1,2, Xi Wu1,2, Yuyu Xiong1,2, Qinghe Xing3, Lin He1,2,3(), Shengying Qin1,2()
1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; 2. Shanghai Genome Pilot Institutes for Genomics and Human Health, Shanghai 200030, China; 3. Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population, and heritability of up to 80%. Drug therapy is an important approach to treating the disease. However, the curative effect of antipsychotic is far from satisfactory in terms of tolerability and side effects. Many studies have indicated that about 30% of the patients exhibit little or no improvements associated with antipsychotics. The response of individual patients who are given the same dose of the same drug varies considerably. In addition, antipsychotic drugs are often accompanied by adverse drug reactions (ADRs), which can cause considerable financial loss in addition to the obvious societal harm. So, it is strongly recommended that personalized medicine should be implemented both to improve drug efficacy and to minimize adverse events and toxicity. There is therefore a need for pharmacogenomic studies into the factors affecting response of schizophrenia patients to antipsychotic drugs to provide informed guidance for clinicians. Individual differences in drug response is due to a combination of many complex factors including ADEM (absorption, distribution, metabolism, excretion) process, transporting, binding with receptor and intracellular signal transduction. Pharmacogenetic and pharmacogenomic studies have successfully identified genetic variants that contribute to this interindividual variability in antipsychotics response. In addition, epigenetic factors such as methylation of DNA and regulation by miRNA have also been reported to play an important role in the complex interactions between the multiple genes and environmental factors which influence individual drug response phenotypes in patients. In this review, we will focus on the latest research on polymorphisms of candidate genes that code for drug metabolic enzymes (CYP2D6, CYP1A2, CYP3A4, etc.), drug transporters (mainly ABCB1) and neurotransmitter receptors (dopamine receptors and serotonin receptors, etc.). We also discuss the genome-wide pharmacogenomic study of schizophrenia and review the current state of knowledge on epigenetics and potential clinical applications.

Keywords pharmacogenomics      epigenetics      schizophrenia      antipsychotics     
Corresponding Authors: He Lin,; Qin Shengying,   
Issue Date: 05 June 2013
URL:     OR
Main contentButyrophenones, phenothiazines thioxanthenesClozapine, olanzapine, risperidone, quetiapine, ziprasidone, etc.
Calming effectPowerfulWeaker (except clozapine)
Receptor targetsNarrow, mainly D2 receptorsMultitarget, D2 receptors and serotonin receptors
High prolactinCommonLess common(except risperidone)
EfficacyGood [13]Equivalent or superior [14,15]
Positive symptomsGood efficacyGood efficacy
Negative symptomsWeaker efficacyBetter efficacy
Cognitive symptomsWeaker efficacyBetter efficacy
Extrapyramidal symptomsSeriousLight
Tardive dyskinesiaCommonRare
Effective doseLarge dosageGenerally small
Weight gainObviousMore obvious(except ziprasidone)
Metabolic syndromeCommon, higher risk [16]Rare, lower risk
Tab.1  A summary of the first-generation antipsychotic medications (FGAs) and second-generation antipsychotic medications (SGAs) [-]
GenePolymorphismSample sizePAssociationReference
ABCB11236C/T130 Chinese patientsP = 0.021Patients with the TT genotype showed greater improvement [45]
3435T116 patientsNo reportPatients on olanzapine homozygous for ABCB1 3435T had more significant social and clinical needs [46]
3435T/2677T/1236T46 white patientsP = 0.026Patients homozygous for the ABCB1 3435T/2677T/1236T haplotype had significantly lower dose-corrected plasma concentrations of 9-hydroxyrisperidone [22]
3435T/2677T/1236T46 white patientsP = 0.028Patients homozygous for the ABCB1 3435T/2677T/1236T haplotype had significantly active moiety [22]
c.3435CC40 men and 20 women-Require higher clozapine doses to achieve the same plasma concentrations as CT or TT patients [47]
3435 T allele and 2667 T-3435 T haplotype83 drug-naive patients-More frequent among subjects without extrapyramidal syndromes [24]
1236T/2677T/3435T haplotype37 white outpatients (10 smokers and 27 nonsmokers)P = 0.018Had higher serum and cerebrospinal fluid olanzapine concentrations [48]
2677T101 previously non-medicated female patientsP<0.001Significantly associated with greater increase in fasting glucose level in blood after olanzapine/ risperidone treatment [49]
3435T101 previously non-medicated female patientsP = 0.028Significantly associated with greater increase in fasting glucose level in blood after olanzapine/ risperidone treatment [49]
2677G/A23 healthy Chinese subjects-May play a role in risperidone pharmacokinetics, needs further studies [50]
5-HT2C-759T101 previously non-medicated female patientsP = 0.03, P = 0.046 and P = 0.045, respectivelyGreater increase in waist circumference, fasting glucose level and triglyceride level in blood after olanzapine/ risperidone treatment [49]
UGT1A4142T/G121 patients-Predicted a 5.1-fold higher olanzapine plasma level in a non-smoking female patient not carrying the variants compared to a smoking man treated with the same dose but heterozygous for UGT1A4 142T / G SNP [51]
Tab.2  Associations of genetic variants with response to antipsychotics
1 Schultze-Lutter F. Subjective symptoms of schizophrenia in research and the clinic: the basic symptom concept. Schizophr Bull 2009; 35(1): 5-8
doi: 10.1093/schbul/sbn139 pmid:19074497
2 Fletcher PC, Frith CD. Perceiving is believing: a Bayesian approach to explaining the positive symptoms of schizophrenia. Nat Rev Neurosci 2009; 10(1): 48-58
doi: 10.1038/nrn2536 pmid:19050712
3 Phan SV, Kreys TJ. Adjunct mirtazapine for negative symptoms of schizophrenia. Pharmacotherapy 2011; 31(10): 1017-1030
doi: 10.1592/phco.31.10.1017 pmid:21950644
4 Hovington CL, Lepage M. Neurocognition and neuroimaging of persistent negative symptoms of schizophrenia. Expert Rev Neurother 2012; 12(1): 53-69
doi: 10.1586/ern.11.173 pmid:22243045
5 Zhang JP, Malhotra AK. Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction. Expert Opin Drug Metab Toxicol 2011; 7(1): 9-37
doi: 10.1517/17425255.2011.532787 pmid:21162693
6 Arranz MJ, de Leon J. Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol Psychiatry 2007; 12(8): 707-747
doi: 10.1038/ pmid:17549063
7 Hamburg MA, Collins FS. The path to personalized medicine. N Engl J Med 2010; 363(4): 301-304
doi: 10.1056/NEJMp1006304 pmid:20551152
8 Shi Y, Li Z, Xu Q, Wang T, Li T, Shen J, Zhang F, Chen J, Zhou G, Ji W, Li B, Xu Y, Liu D, Wang P, Yang P, Liu B, Sun W, Wan C, Qin S, He G, Steinberg S, Cichon S, Werge T, Sigurdsson E, Tosato S, Palotie A, N?then MM, Rietschel M, Ophoff RA, Collier DA, Rujescu D, Clair DS, Stefansson H, Stefansson K, Ji J, Wang Q, Li W, Zheng L, Zhang H, Feng G, He L. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nat Genet 2011; 43(12): 1224-1227
doi: 10.1038/ng.980 pmid:22037555
9 Yue WH, Wang HF, Sun LD, Tang FL, Liu ZH, Zhang HX, Li WQ, Zhang YL, Zhang Y, Ma CC, Du B, Wang LF, Ren YQ, Yang YF, Hu XF, Wang Y, Deng W, Tan LW, Tan YL, Chen Q, Xu GM, Yang GG, Zuo XB, Yan H, Ruan YY, Lu TL, Han X, Ma XH, Wang Y, Cai LW, Jin C, Zhang HY, Yan J, Mi WF, Yin XY, Ma WB, Liu Q, Kang L, Sun W, Pan CY, Shuang M, Yang FD, Wang CY, Yang JL, Li KQ, Ma X, Li LJ, Yu X, Li QZ, Huang X, Lv LX, Li T, Zhao GP, Huang W, Zhang XJ, Zhang D. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet 2011; 43(12): 1228-1231
doi: 10.1038/ng.979 pmid:22037552
10 Leucht S, Heres S, Kissling W, Davis JM. Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacol 2011; 14(2): 269-284
doi: 10.1017/S1461145710001380 pmid:21208500
11 Foussias G, Remington G. Antipsychotics and schizophrenia: from efficacy and effectiveness to clinical decision-making. Can J Psychiatry 2010; 55(3): 117-125
12 Hill SK, Bishop JR, Palumbo D, Sweeney JA. Effect of second-generation antipsychotics on cognition: current issues and future challenges. Expert Rev Neurother 2010; 10(1): 43-57
doi: 10.1586/ern.09.143 pmid:20021320
13 Guo X, Fang M, Zhai J, Wang B, Wang C, Hu B, Sun X, Lv L, Lu Z, Ma C, Guo T, Xie S, Twamley EW, Jin H, Zhao J. Effectiveness of maintenance treatments with atypical and typical antipsychotics in stable schizophrenia with early stage: 1-year naturalistic study. Psychopharmacology (Berl) 2011; 216(4): 475-484
doi: 10.1007/s00213-011-2242-3 pmid:21369751
14 Citrome L. A systematic review of meta-analyses of the efficacy of oral atypical antipsychotics for the treatment of adult patients with schizophrenia. Expert Opin Pharmacother 2012; 13(11): 1545-1573
doi: 10.1517/14656566.2011.626769 pmid:21999805
15 Crossley NA, Constante M, McGuire P, Power P. Efficacy of atypical v. typical antipsychotics in the treatment of early psychosis: meta-analysis. Br J Psychiatry 2010; 196(6): 434-439
doi: 10.1192/bjp.bp.109.066217 pmid:20513851
16 De Hert M, Schreurs V, Sweers K, Van Eyck D, Hanssens L, Sinko S, Wampers M, Scheen A, Peuskens J, van Winkel R. Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. Schizophr Res 2008; 101(1-3): 295-303
doi: 10.1016/j.schres.2008.01.028 pmid:18299188
17 Guengerich FP. Cytochrome p450 and chemical toxicology. Chem Res Toxicol 2008; 21(1): 70-83
doi: 10.1021/tx700079z pmid:18052394
18 Cacabelos R, Hashimoto R, Takeda M. Pharmacogenomics of antipsychotics efficacy for schizophrenia. Psychiatry Clin Neurosci 2011; 65(1): 3-19
doi: 10.1111/j.1440-1819.2010.02168.x pmid:21265934
19 Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockm?ller J. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004; 9(5): 442-473
doi: 10.1038/ pmid:15037866
20 Teh LK, Bertilsson L. Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance. Drug Metab Pharmacokinet 2012; 27(1): 55-67
doi: 10.2133/dmpk.DMPK-11-RV-121 pmid:22185816
21 Yasui-Furukori N, Mihara K, Takahata T, Suzuki A, Nakagami T, De Vries R, Tateishi T, Kondo T, Kaneko S. Effects of various factors on steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone: lack of impact of MDR-1 genotypes. Br J Clin Pharmacol 2004; 57(5): 569-575
doi: 10.1111/j.1365-2125.2003.02061.x pmid:15089809
22 Gunes A, Spina E, Dahl ML, Scordo MG. ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone and risperidone active moiety. Ther Drug Monit 2008; 30(5): 628-633
doi: 10.1097/FTD.0b013e3181858ca9 pmid:18708991
23 Roh HK, Kim CE, Chung WG, Park CS, Svensson JO, Bertilsson L. Risperidone metabolism in relation to CYP2D6*10 allele in Korean schizophrenic patients. Eur J Clin Pharmacol 2001; 57(9): 671-675
doi: 10.1007/s002280100372 pmid:11791898
24 Jovanovi? N, Bo?ina N, Lovri? M, Medved V, Jakovljevi? M, Pele? AM. The role of CYP2D6 and ABCB1 pharmacogenetics in drug-na?ve patients with first-episode schizophrenia treated with risperidone. Eur J Clin Pharmacol 2010; 66(11): 1109-1117
doi: 10.1007/s00228-010-0850-1 pmid:20563569
25 Scordo MG, Spina E, Facciolà G, Avenoso A, Johansson I, Dahl ML. Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology (Berl) 1999; 147(3): 300-305
doi: 10.1007/s002130051171 pmid:10639689
26 Mihara K, Kondo T, Yasui-Furukori N, Suzuki A, Ishida M, Ono S, Kubota T, Iga T, Takarada Y, de Vries R, Kaneko S. Effects of various CYP2D6 genotypes on the steady-state plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, in Japanese patients with schizophrenia. Ther Drug Monit 2003; 25(3): 287-293
doi: 10.1097/00007691-200306000-00006 pmid:12766554
27 Yasui-Furukori N, Mihara K, Kondo T, Kubota T, Iga T, Takarada Y, De Vries R, Kaneko S, Tateishi T. Effects of CYP2D6 genotypes on plasma concentrations of risperidone and enantiomers of 9-hydroxyrisperidone in Japanese patients with schizophrenia. J Clin Pharmacol 2003; 43(2): 122-127
doi: 10.1177/0091270002239819 pmid:12616663
28 Wang L, Yu L, Zhang AP, Fang C, Du J, Gu NF, Qin SY, Feng GY, Li XW, Xing QH, He L. Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia. J Psychopharmacol 2007; 21(8): 837-842
doi: 10.1177/0269881107077357 pmid:17715206
29 Du J, Xu Y, Duan S, Zhang A, Xuan J, Wang L, Yu L, Wang H, Li X, Feng G, He L, Xing Q. A case-control association study between the CYP3A4 and CYP3A5 genes and schizophrenia in the Chinese Han population. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33(7): 1200-1204
doi: 10.1016/j.pnpbp.2009.06.023 pmid:19591893
30 Mahatthanatrakul W, Nontaput T, Ridtitid W, Wongnawa M, Sunbhanich M. Rifampin, a cytochrome P450 3A inducer, decreases plasma concentrations of antipsychotic risperidone in healthy volunteers. J Clin Pharm Ther 2007; 32(2): 161-167
doi: 10.1111/j.1365-2710.2007.00811.x pmid:17381666
31 Mahatthanatrakul W, Sriwiriyajan S, Ridtitid W, Boonleang J, Wongnawa M, Rujimamahasan N, Pipatrattanaseree W. Effect of cytochrome P450 3A4 inhibitor ketoconazole on risperidone pharmacokinetics in healthy volunteers. J Clin Pharm Ther 2012; 37(2): 221-225
doi: 10.1111/j.1365-2710.2011.01271.x pmid:21518375
32 Dai D, Tang J, Rose R, Hodgson E, Bienstock RJ, Mohrenweiser HW, Goldstein JA. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 2001; 299(3): 825-831
33 Du J, Zhang A, Wang L, Xuan J, Yu L, Che R, Li X, Gu N, Lin Z, Feng G, Xing Q, He L. Relationship between response to risperidone, plasma concentrations of risperidone and CYP3A4 polymorphisms in schizophrenia patients. J Psychopharmacol 2010; 24(7): 1115-1120
doi: 10.1177/0269881109104932 pmid:19395426
34 Tiwari AK, Deshpande SN, Rao AR, Bhatia T, Lerer B, Nimgaonkar VL, Thelma BK. Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: III. Lack of association of CYP3A4 and CYP2D6 gene polymorphisms. Schizophr Res 2005; 75(1): 21-26
doi: 10.1016/j.schres.2004.12.011 pmid:15820320
35 Eiermann B, Engel G, Johansson I, Zanger UM, Bertilsson L. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 1997; 44(5): 439-446
doi: 10.1046/j.1365-2125.1997.t01-1-00605.x pmid:9384460
36 Ring BJ, Catlow J, Lindsay TJ, Gillespie T, Roskos LK, Cerimele BJ, Swanson SP, Hamman MA, Wrighton SA. Identification of the human cytochromes P450 responsible for the in vitro formation of the major oxidative metabolites of the antipsychotic agent olanzapine. J Pharmacol Exp Ther 1996; 276(2): 658-666
37 Bozikas VP, Papakosta M, Niopas I, Karavatos A, Mirtsou-Fidani V. Smoking impact on CYP1A2 activity in a group of patients with schizophrenia. Eur Neuropsychopharmacol 2004; 14(1): 39-44
doi: 10.1016/S0924-977X(03)00061-0 pmid:14659985
38 Pavanello S, Pulliero A, Lupi S, Gregorio P, Clonfero E. Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers. Mutat Res 2005; 587(1-2): 59-66
doi: 10.1016/j.mrgentox.2005.08.008 pmid:16188490
39 Murayama N, Soyama A, Saito Y, Nakajima Y, Komamura K, Ueno K, Kamakura S, Kitakaze M, Kimura H, Goto Y, Saitoh O, Katoh M, Ohnuma T, Kawai M, Sugai K, Ohtsuki T, Suzuki C, Minami N, Ozawa S, Sawada J. Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes. J Pharmacol Exp Ther 2004; 308(1): 300-306
doi: 10.1124/jpet.103.055798 pmid:14563787
40 Sachse C, Brockm?ller J, Bauer S, Roots I. Functional significance of a C—>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999; 47(4): 445-449
doi: 10.1046/j.1365-2125.1999.00898.x pmid:10233211
41 Kootstra-Ros JE, Smallegoor W, van der Weide J. The cytochrome P450 CYP1A2 genetic polymorphisms *1F and *1D do not affect clozapine clearance in a group of schizophrenic patients. Ann Clin Biochem 2005; 42(Pt 3): 216-219
doi: 10.1258/0004563053857798 pmid:15949157
42 Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockm?ller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000; 97(7): 3473-3478
doi: 10.1073/pnas.97.7.3473 pmid:10716719
43 Kerb R, Hoffmeyer S, Brinkmann U. ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2. Pharmacogenomics 2001; 2(1): 51-64
doi: 10.1517/14622416.2.1.51 pmid:11258197
44 Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther 2004; 75(1): 13-33
doi: 10.1016/j.clpt.2003.09.012 pmid:14749689
45 Xing Q, Gao R, Li H, Feng G, Xu M, Duan S, Meng J, Zhang A, Qin S, He L. Polymorphisms of the ABCB1 gene are associated with the therapeutic response to risperidone in Chinese schizophrenia patients. Pharmacogenomics 2006; 7(7): 987-993
doi: 10.2217/14622416.7.7.987 pmid:17054409
46 Alenius M, Wadelius M, Dahl ML, Hartvig P, Lindstr?m L, Hammarlund-Udenaes M. Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting. J Psychiatr Res 2008; 42(11): 884-893
doi: 10.1016/j.jpsychires.2007.10.007 pmid:18086475
47 Consoli G, Lastella M, Ciapparelli A, Catena Dell’Osso M, Ciofi L, Guidotti E, Danesi R, Dell’Osso L, Del Tacca M, Di Paolo A. ABCB1 polymorphisms are associated with clozapine plasma levels in psychotic patients. Pharmacogenomics 2009; 10(8): 1267-1276
doi: 10.2217/pgs.09.51 pmid:19663671
48 Skogh E, Sj?din I, Josefsson M, Dahl ML. High correlation between serum and cerebrospinal fluid olanzapine concentrations in patients with schizophrenia or schizoaffective disorder medicating with oral olanzapine as the only antipsychotic drug. J Clin Psychopharmacol 2011; 31(1): 4-9
doi: 10.1097/JCP.0b013e318204d9e2 pmid:21192135
49 Kuzman MR, Medved V, Bozina N, Grubi?in J, Jovanovic N, Sertic J. Association study of MDR1 and 5-HT2C genetic polymorphisms and antipsychotic-induced metabolic disturbances in female patients with schizophrenia. Pharmacogenomics J 2011; 11(1): 35-44
doi: 10.1038/tpj.2010.7 pmid:20195292
50 Xiang Q, Zhao X, Zhou Y, Duan JL, Cui YM. Effect of CYP2D6, CYP3A5, and MDR1 genetic polymorphisms on the pharmacokinetics of risperidone and its active moiety. J Clin Pharmacol 2010; 50(6): 659-666
doi: 10.1177/0091270009347867 pmid:20332423
51 Ghotbi R, Mannheimer B, Aklillu E, Suda A, Bertilsson L, Eliasson E, Osby U. Carriers of the UGT1A4 142T>G gene variant are predisposed to reduced olanzapine exposure—an impact similar to male gender or smoking in schizophrenic patients. Eur J Clin Pharmacol 2010; 66(5): 465-474
doi: 10.1007/s00228-009-0783-8 pmid:20143052
52 Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, Lee MLT, Xiao T, Papp A, Wang DX, Sadée W. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci USA 2007; 104(51): 20552-20557
doi: 10.1073/pnas.0707106104 pmid:18077373
53 Ikeda M, Yamanouchi Y, Kinoshita Y, Kitajima T, Yoshimura R, Hashimoto S, O’Donovan MC, Nakamura J, Ozaki N, Iwata N. Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia. Pharmacogenomics 2008; 9(10): 1437-1443
doi: 10.2217/14622416.9.10.1437 pmid:18855532
54 Zahari Z, Teh LK, Ismail R, Razali SM. Influence of DRD2 polymorphisms on the clinical outcomes of patients with schizophrenia. Psychiatr Genet 2011; 21(4): 183-189
doi: 10.1097/YPG.0b013e3283437250 pmid:21206399
55 Xing Q, Qian X, Li H, Wong S, Wu S, Feng G, Duan S, Xu M, Gao R, Qin W, Gao J, Meng J, He L. The relationship between the therapeutic response to risperidone and the dopamine D2 receptor polymorphism in Chinese schizophrenia patients. Int J Neuropsychopharmacol 2007; 10(5): 631-637
doi: 10.1017/S146114570600719X pmid:17105675
56 Lundstrom K, Turpin MP. Proposed schizophrenia-related gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest virus system. Biochem Biophys Res Commun 1996; 225(3): 1068-1072
doi: 10.1006/bbrc.1996.1296 pmid:8780735
57 Lane HY, Hsu SK, Liu YC, Chang YC, Huang CH, Chang WH. Dopamine D3 receptor Ser9Gly polymorphism and risperidone response. J Clin Psychopharmacol 2005; 25(1): 6-11
doi: 10.1097/ pmid:15643094
58 Xuan JK, Zhao XZ, He G, Yu L, Wang L, Tang W, Li XW, Gu NF, Feng GY, Xing QH, He L. Effects of the dopamine D3 receptor (DRD3) gene polymorphisms on risperidone response: a pharmacogenetic study. Neuropsychopharmacology 2008; 33(2): 305-311
doi: 10.1038/sj.npp.1301418 pmid:17429404
59 Travis MJ, Busatto GF, Pilowsky LS, Mulligan R, Acton PD, Gacinovic S, Mertens J, Terrière D, Costa DC, Ell PJ, Kerwin RW. 5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150. Br J Psychiatry 1998; 173(3): 236-241
doi: 10.1192/bjp.173.3.236 pmid:9926100
60 Parsons MJ, D’Souza UM, Arranz MJ, Kerwin RW, Makoff AJ. The-1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity. Biol Psychiatry 2004; 56(6): 406-410
doi: 10.1016/j.biopsych.2004.06.020 pmid:15364038
61 Myers RL, Airey DC, Manier DH, Shelton RC, Sanders-Bush E. Polymorphisms in the regulatory region of the human serotonin 5-HT2A receptor gene (HTR2A) influence gene expression. Biol Psychiatry 2007; 61(2): 167-173
doi: 10.1016/j.biopsych.2005.12.018 pmid:16697352
62 Benmessaoud D, Hamdani N, Boni C, Ramoz N, Hamon M, Kacha F, Gorwood P. Excess of transmission of the G allele of the‐1438A/G polymorphism of the 5‐HT(2A) receptor gene in patients with schizophrenia responsive to antipsychotics. BMC Psychiatry . 2008 May 30; 8:40
doi: 10.1186/1471-244X-8-40 pmid:18513383
63 Gunes A, Melkersson KI, Scordo MG, Dahl ML. Association between HTR2C and HTR2A polymorphisms and metabolic abnormalities in patients treated with olanzapine or clozapine. J Clin Psychopharmacol 2009; 29(1): 65-68
doi: 10.1097/JCP.0b013e31819302c3 pmid:19142110
64 Popp J, Leucht S, Heres S, Steimer W. DRD4 48 bp VNTR but not 5-HT 2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain. Pharmacogenomics J 2009; 9(1): 71-77
doi: 10.1038/tpj.2008.5 pmid:18332898
65 Hill MJ, Reynolds GP. Functional consequences of two HTR2C polymorphisms associated with antipsychotic-induced weight gain. Pharmacogenomics 2011; 12(5): 727-734
doi: 10.2217/pgs.11.16 pmid:21391883
66 Davies MA, Setola V, Strachan RT, Sheffler DJ, Salay E, Hufeisen SJ, Roth BL. Pharmacologic analysis of non-synonymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies. Pharmacogenomics J 2006; 6(1): 42-51
doi: 10.1038/sj.tpj.6500342 pmid:16314884
67 Wang L, Fang C, Zhang A, Du J, Yu L, Ma J, Feng G, Xing Q, He L. The -1019 C/G polymorphism of the 5-HT(1)A receptor gene is associated with negative symptom response to risperidone treatment in schizophrenia patients. J Psychopharmacol 2008; 22(8): 904-909
doi: 10.1177/0269881107081522 pmid:18308786
68 Gu B, Wang L, Zhang AP, Ma G, Zhao XZ, Li HF, Feng GY, He L, Xing QH. Association between a polymorphism of the HTR3A gene and therapeutic response to risperidone treatment in drug-naive Chinese schizophrenia patients. Pharmacogenet Genomics 2008; 18(8): 721-727
doi: 10.1097/FPC.0b013e32830500e2 pmid:18622264
69 Wei Z, Wang L, Xuan J, Che R, Du J, Qin S, Xing Y, Gu B, Yang L, Li H, Li J, Feng G, He L, Xing Q. Association analysis of serotonin receptor 7 gene (HTR7) and risperidone response in Chinese schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33(3): 547-551
doi: 10.1016/j.pnpbp.2009.02.008 pmid:19233240
70 Houston JP, Kohler J, Bishop JR, Ellingrod VL, Ostbye KM, Zhao F, Conley RR, Poole Hoffmann V, Fijal BA. Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia. J Clin Psychiatry 2012; 73(8): 1077-1086
doi: 10.4088/JCP.11m06916 pmid:22967772
72 Zai CC, Hwang RW, De Luca V, Müller DJ, King N, Zai GC, Remington G, Meltzer HY, Lieberman JA, Potkin SG, Kennedy JL. Association study of tardive dyskinesia and twelve DRD2 polymorphisms in schizophrenia patients. Int J Neuropsychopharmacol 2007; 10(5): 639-651
doi: 10.1017/S1461145706007152 pmid:16959057
73 McClay JL, Adkins DE, Aberg K, Stroup S, Perkins DO, Vladimirov VI, Lieberman JA, Sullivan PF, van den Oord EJ. Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics. Mol Psychiatry 2011; 16(1): 76-85
doi: 10.1038/mp.2009.89 pmid:19721433
74 Adkins DE, Aberg K, McClay JL, Bukszár J, Zhao Z, Jia P, Stroup TS, Perkins D, McEvoy JP, Lieberman JA, Sullivan PF, van den Oord EJ. Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. Mol Psychiatry 2011; 16(3): 321-332
doi: 10.1038/mp.2010.14 pmid:20195266
75 Ingelman-Sundberg M, Gomez A. The past, present and future of pharmacoepigenomics. Pharmacogenomics 2010; 11(5): 625-627
doi: 10.2217/pgs.10.59 pmid:20415549
76 Baker EK, Johnstone RW, Zalcberg JR, El-Osta A. Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs. Oncogene 2005; 24(54): 8061-8075
doi: 10.1038/sj.onc.1208955 pmid:16091741
77 Hammons GJ, Yan-Sanders Y, Jin B, Blann E, Kadlubar FF, Lyn-Cook BD. Specific site methylation in the 5′-flanking region of CYP1A2 interindividual differences in human livers. Life Sci 2001; 69(7): 839-845 11487095
doi: 10.1016/S0024-3205(01)01175-4
78 Tsuchiya Y, Nakajima M, Takagi S, Taniya T, Yokoi T. MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res 2006; 66(18): 9090-9098
doi: 10.1158/0008-5472.CAN-06-1403 pmid:16982751
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