Skip to main content
SpringerLink
Log in

Pharmacogenomics: Clinical Perspective, Strategies, and Challenges

  • Chapter
  • First Online:
Translational Bioinformatics and Its Application

Part of the book series: Translational Medicine Research ((TRAMERE))

Abstract

Pharmacogenomics (PGx) defines the genetic basis of variability among individuals in response to drugs. It is an emerging discipline of medical science and is now a challenging and applied area of medical research. Several factors influence the efficacy and toxicity of drugs such as environmental factors, age, weight, gender, liver and kidney function, and applied drug therapy. Another crucial factor that influences the drug response of a patient is the genetic makeup of the patient. Polymorphism affects the drug efficacy, bioavailability, and toxicity. Human Genome Project (HGP) has provided a foundation for PGx study by identifying genes related to a disease. PGx knowledge derived from genetic profiling and associated drug response must be translated into clinical applications. A drug label contains information about PGx biomarker and drug related to a therapeutic area and also provides specific information for safe and effective medication based on a biomarker. PGx drugs have improved therapeutic response and also avoid events of adverse drug reactions (ADRs). There are some important ethical, social justice, and economic issues related to PGx which create hurdles in the drug development via PGx. The objective of this chapter is to discuss the basic principle of PGx and its application and also to put forward the ethical, social, technological, and economic challenges in the way of PGx. In spite of many challenges, it is expected that PGx may offer significant promises toward the goal of personalized medicine in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abraham A, Varatharajan S, Karathedath S, Philip C, Lakshmi KM, Jayavelu AK, Mohanan E, Janet NB, Srivastava VM, Shaji RV, Zhang W, Abraham A, Viswabandya A, George B, Chandy M, Srivastava A, Mathews V, Balasubramanian P. RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia. Pharmacogenomics. 2015;16:877–90.

    Article  CAS  PubMed  Google Scholar 

  • Ageno W, Johnson J, Nowacki B, Turpie AG. A computer generated induction system for hospitalized patients starting on oral anticoagulant therapy. Thromb Haemost. 2000;83:849–52.

    CAS  PubMed  Google Scholar 

  • Agúndez JA, Blanca M, Cornejo-García JA, García-Martín E. Pharmacogenomics of cyclooxygenases. Pharmacogenomics. 2015;16:501–22.

    Article  PubMed  CAS  Google Scholar 

  • Alomar MJ. Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm J. 2014;22:83–94.

    Article  PubMed  Google Scholar 

  • American Nurse Today. The role of pharmacogenomics in cancer. n.d. http://www.americannursetoday.com/the-role-of-pharmacogenomics-in-cancer. Accessed 12 Sept 2015

  • Ansari M, Krajinovic M. Pharmacogenomics in cancer treatment defining genetic bases for inter-individual differences in responses to chemotherapy. Curr Opin Pediatr. 2007;19:15–22.

    Article  PubMed  Google Scholar 

  • Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  • Bavarva JH, Bavarva MJ, Karunasena E. Next in line in next-generation sequencing: are we there yet? Pharmacogenomics. 2015;16:1–4.

    Article  CAS  PubMed  Google Scholar 

  • Becker ML, Kallewaard M, Caspers PW, Schalekamp T, Stricker BH. Potential determinants of drug-drug interaction associated dispensing in community pharmacies. Drug Saf. 2005;28:371–8.

    Article  PubMed  Google Scholar 

  • Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmüller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R, for “Precision Medicine and Pharmacometabolomics Task Group”-Metabolomics Society Initiative. Metabolomics enables precision medicine: “A white paper, community perspective”. Metabolomics. 2016;12:149.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005;120:21–4.

    Article  CAS  PubMed  Google Scholar 

  • Berg AO. The CDC’s EGAPP initiative: evaluating the clinical evidence for genetic tests. Am Fam Physician. 2009;80:1218.

    PubMed  Google Scholar 

  • Biobank. About UK Biobank. n.d. http://www.ukbiobank.ac.uk/about-biobank-uk. Accessed 25 July 2015.

  • Borroni RG. Role of dermatology in pharmacogenomics: drug-induced skin injury. Pharmacogenomics. 2015;16:401–12.

    Article  CAS  PubMed  Google Scholar 

  • Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3:229–43.

    Article  CAS  PubMed  Google Scholar 

  • Budimir D, Polasek O, Marusić A, Kolcić I, Zemunik T, Boraska V, Jeroncić A, Boban M, Campbell H, Rudan I. Ethical aspects of human biobanks: a systematic review. Croat Med J. 2011;52:262–79.

    Article  PubMed  PubMed Central  Google Scholar 

  • Burt T, Dhillon S. Pharmacogenomics in early-phase clinical development. Pharmacogenomics. 2013;14:1085–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burt T, Nandal S. Pharmacometabolomics in early-phase clinical development. Clin Transl Sci. 2016;9:128–38.

    Article  CAS  PubMed  Google Scholar 

  • Chan A, Tan SH, Wong CM, Yap KY, Ko Y. Clinically significant drug-drug interactions between oral anticancer agents and nonanticancer agents: a Delphi survey of oncology pharmacists. Clin Ther. 2009;2:2379–86.

    Article  CAS  Google Scholar 

  • Cho WC. Recent progress in genetic variants associated with cancer and their implications in diagnostics development. Expert Rev Mol Diagn. 2010;10:699–703.

    Article  CAS  PubMed  Google Scholar 

  • Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010;11:415–25.

    Article  CAS  PubMed  Google Scholar 

  • Collins SL, Carr DF, Pirmohamed M. Advances in the pharmacogenomics of adverse drug reactions. Drug Saf. 2016;39:15–27.

    Article  CAS  PubMed  Google Scholar 

  • Cox NJ, Gamazon ER, Wheeler HE, Dolan ME. Clinical translation of cell-based pharmacogenomic discovery. Clin Pharmacol Ther. 2012;92:425–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • CPIC. Clinical Pharmacogenetics Implementation Consortium. n.d. https://cpicpgx.org. Accessed 03 May 2016.

  • De Souza JA, Olopade OI. CYP2D6 genotyping and tamoxifen: an unfinished story in the quest for personalized medicine. Semin Oncol. 2011;38:263–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Everett JR. Pharmacometabonomics in humans: a new tool for personalized medicine. Pharmacogenomics. 2015;16:737–54.

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, He X, Yang Y, Chao D, Lazarus LH, Xia Y. Current research on opioid receptor function. Curr Drug Targets. 2012;13:230–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genetic Alliance Registry and Biobank. Overview. n.d. http://biobank.org/biobanks. Accessed 28 July 2015.

  • Genetic Home Reference What is Pharmacogenomics? n.d. http://ghr.nlm.nih.gov/handbook/genomicresearch/pharmacogenomics. Accessed 28 July 2015.

  • GENEWIZ PGxOne™. Comprehensive pharmacogenomics test. n.d. http://www.genewiz.com/public/PGxOne-pharmacogenomics-test.aspx. Accessed 20 July 2015.

  • Gregersen PK, Olsson LM. Recent advances in the genetics of autoimmune disease. Annu Rev Immunol. 2009;27:363–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gurdasani D, Carstensen T, Tekola-Ayele F, Pagani L, Tachmazidou I, Hatzikotoulas K, Karthikeyan S, Iles L, Pollard MO, Choudhury A, Ritchie GR, Xue Y, Asimit J, Nsubuga RN, Young EH, Pomilla C, Kivinen K, Rockett K, Kamali A, Doumatey AP, Asiki G, Seeley J, Sisay-Joof F, Jallow M, Tollman S, Mekonnen E, Ekong R, Oljira T, Bradman N, Bojang K, Ramsay M, Adeyemo A, Bekele E, Motala A, Norris SA, Pirie F, Kaleebu P, Kwiatkowski D, Tyler-Smith C, Rotimi C, Zeggini E, Sandhu MS. The African genome variation project shapes medical genetics in Africa. Nature. 2015;517:327–32.

    Article  CAS  PubMed  Google Scholar 

  • Haga SB, Moaddeb J. Potential use of auxiliary labels to promote patient awareness of pharmacogenetic testing. Pharmacogenomics. 2015;16:299–301.

    Article  CAS  PubMed  Google Scholar 

  • He B, Pan Y, Cho WC, Xu Y, Gu L, Nie Z, Chen L, Song G, Gao T, Li R, Wang S. The association between four genetic variants in microRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and cancer risk: evidence from published studies. PLoS One. 2012;7(11):e49032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Y, Hoskins JM, Clark S, Campbell NH, Wagner K, Motsinger-Reif AA, McLeod HL. Accuracy of SNPs to predict risk of HLA alleles associated with drug-induced hypersensitivity events across racial groups. Pharmacogenomics. 2015;16:817–24.

    Article  CAS  PubMed  Google Scholar 

  • Hertz DL, McLeod HL. Use of pharmacogenetics for predicting cancer prognosis and treatment exposure, response and toxicity. J Hum Genet. 2013;58:346–52.

    Article  CAS  PubMed  Google Scholar 

  • Hess GP, Fonseca E, Scott R, Fagerness J. Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders. Genet Res (Camb). 2015;97:e13. doi:10.1017/S0016672315000099.

    Article  Google Scholar 

  • Hicks JK, Gonzalez BE, Zembillas AS, Kusick K, Murthy S, Raja S, Gordon SM, Hanna R. Invasive Aspergillus infection requiring lobectomy in a CYP2C19 rapid metabolizer with subtherapeutic voriconazole concentrations. Pharmacogenomics. 2016;17:663–7.

    Article  CAS  PubMed  Google Scholar 

  • Hirsh J, Dalen J, Anderson DR, Poller L, Bussey H, Ansell J, Deykin D. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 2001;119:8S–21S.

    Article  CAS  PubMed  Google Scholar 

  • Hu Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S. Herb-drug interactions: a literature review. Drugs. 2005;65:1239–82.

    Article  CAS  PubMed  Google Scholar 

  • Huang Q, Aa J, Jia H, Xin X, Tao C, Liu L, Zou B, Song Q, Shi J, Cao B, Yong Y, Wang G, Zhou G. A pharmacometabonomic approach to predicting metabolic phenotypes and pharmacokinetic parameters of atorvastatin in healthy volunteers. J Proteome Res. 2015;14:3970–81.

    Article  CAS  PubMed  Google Scholar 

  • IGSR. Supporting the 1000 genomes data. n.d. http://www.internationalgenome.org. Accessed 01 May 2016.

  • IGSR: The International Genome Sample Resource. n.d. http://www.1000genomes.org/about. Accessed 02 May 2016.

  • Ingelman-Sundberg M, Rodriguez-Antona C. Pharmacogenetics of drug metabolizing enzymes: implications for a safer and more effective drug therapy. Philos Trans R Soc Lond Ser B Biol Sci. 2005;360:1563–70.

    Article  CAS  Google Scholar 

  • Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007;116:496–526.

    Article  CAS  PubMed  Google Scholar 

  • International HapMap Consortium. The international HapMap project. Nature. 2003;426:789–96.

    Article  CAS  Google Scholar 

  • International HapMap Project. n.d. http://www.hapmap.org. Accessed 02 May 2016.

  • James LP. Metabolomics: integration of a new “omics” with clinical pharmacology. Clin Pharmacol Ther. 2013;94:547–51.

    Article  CAS  PubMed  Google Scholar 

  • Jarjour S, Barrette M, Normand V, Rouleau JL, Dubé MP, de Denus S. Genetic markers associated with cutaneous adverse drug reactions to allopurinol: a systematic review. Pharmacogenomics. 2015;16:755–67.

    Article  CAS  PubMed  Google Scholar 

  • Javorský M, Gotthardová I, Klimčáková L, Kvapil M, Židzik J, Schroner Z, Doubravová P, Gaľa I, Dravecká I, Tkáč I. A missense variant in GLP1R gene is associated with the glycemic response to treatment with gliptins. Diabetes Obes Metab. 2016;18:941. doi:10.1111/dom.12682.

    Article  PubMed  CAS  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  • Johnson JA, Burkley BM, Langaee TY, Clare-Salzler MJ, Klein TE, Altman RB. Implementing personalized medicine: development of a cost-effective custom pharmacogenetics genotyping array. Clin Pharmacol Ther. 2012;92:437–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jorde LB, Wooding SP. Genetic variation, classification and ‘race’. Nat Genet. 2004;36:S28–33.

    Article  CAS  PubMed  Google Scholar 

  • Kaddurah-Daouk R, Weinshilboum R, Pharmacometabolomics Research Network. Metabolomic signatures for drug response phenotypes-pharmacometabolomics enables precision medicine. Clin Pharmacol Ther. 2015;98:71–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009;158:693–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaniwa N, Saito Y. Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury. J Hum Genet. 2013;58:317–26.

    Article  CAS  PubMed  Google Scholar 

  • Kap EJ, Popanda O, Chang-Claude J. Nucleotide excision repair and response and survival to chemotherapy in colorectal cancer patients. Pharmacogenomics. 2016;17:755–94.

    Article  CAS  PubMed  Google Scholar 

  • Khoury MJ, Coates RJ, Evans JP. Evidence-based classification of recommendations on use of genomic tests in clinical practice: dealing with insufficient evidence. Genitourin Med. 2010;12:680–3.

    Article  Google Scholar 

  • Kimura S. Invasive Aspergillosis in Hematological Patients. Med Mycol J. 2016;57:77–88.

    Article  Google Scholar 

  • Kitzmiller JP, Groen DK, Phelps MA, Sadee W. Pharmacogenomic testing: relevance in medical practice: why drugs work in some patients but not in others. Cleve Clin J Med. 2011;78:243–57.

    Article  PubMed  PubMed Central  Google Scholar 

  • Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41:67–76.

    Article  CAS  PubMed  Google Scholar 

  • Kothari A, Hittelman WN, Chambers TC. Cell cycle-dependent mechanisms underlie Vincristine-induced death of primary acute lymphoblastic leukemia cells. Cancer Res. 2016;76:3553. doi:10.1158/0008-5472.CAN-15-2104.

    Article  CAS  PubMed  Google Scholar 

  • Kushner FG, Hand M, Smith Jr SC, King 3rd SB, Anderson JL, Antman EM, Bailey SR, Bates ER, Blankenship JC, Casey Jr DE, Green LA, Hochman JS, Jacobs AK, Krumholz HM, Morrison DA, Ornato JP, Pearle DL, Peterson ED, Sloan MA, Whitlow PL, Williams DO. Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54:2205–41.

    Article  PubMed  Google Scholar 

  • Lam YW. Scientific challenges and implementation barriers to translation of pharmacogenomics in clinical practice. ISRN Pharmacol. 2013;2013:1. doi:10.1155/2013/641089.

    Article  Google Scholar 

  • Leblhuber F, Neubauer C, Peichl M, Reisecker F, Steinparz FX, Windhager E, Dienstl E. Age and sex differences of dehydroepiandrosterone sulfate (DHEAS) and cortisol (CRT) plasma levels in normal controls and Alzheimer’s disease (AD). Psychopharmacology. 1993;111:23–6.

    Article  CAS  PubMed  Google Scholar 

  • Lee MT, Klein TE. Pharmacogenetics of warfarin: challenges and opportunities. J Hum Genet. 2013;58:334–8.

    Article  CAS  PubMed  Google Scholar 

  • Lesko LJ. The critical path of warfarin dosing: finding an optimal dosing strategy using pharmacogenetics. Clin Pharmacol Ther. 2008;84:301–3.

    Article  CAS  PubMed  Google Scholar 

  • Lin E, Lane HY. Genome-wide association studies in pharmacogenomics of antidepressants. Pharmacogenomics. 2015;16:555–66.

    Article  CAS  PubMed  Google Scholar 

  • Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Jänne PA, Stephens PJ. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012;18:382–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Lopez E, Gutierrez-Camino A, Astigarraga I, Navajas A, Echebarria-Barona A, Garcia-Miguel P, Garcia de Andoin N, Lobo C, Guerra-Merino I, Martin-Guerrero I, Garcia-Orad A. Vincristine pharmacokinetics pathway and neurotoxicity during early phases of treatment in pediatric acute lymphoblastic leukemia. Pharmacogenomics. 2016;17:731–41.

    Article  CAS  PubMed  Google Scholar 

  • Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007;76:391–6.

    PubMed  Google Scholar 

  • Ma Q, Lu AY. Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev. 2011;63:437–59.

    Article  CAS  PubMed  Google Scholar 

  • Ma JD, Lee KC, Kuo GM. Clinical application of pharmacogenomics. J Pharm Pract. 2012;25:417–27.

    Article  PubMed  Google Scholar 

  • Magro L, Moretti U, Leone R. Epidemiology and characteristics of adverse drug reactions caused by drug-drug interactions. Expert Opin Drug Saf. 2012;11:83–94.

    Article  CAS  PubMed  Google Scholar 

  • Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57:6–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marian AJ, Belmont J. Strategic approaches to unraveling genetic causes of cardiovascular diseases. Circ Res. 2011;108:1252–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marsh S, King CR, Van Booven DJ, Revollo JY, Gilman RH, McLeod HL. Pharmacogenomic assessment of Mexican and Peruvian populations. Pharmacogenomics. 2015;16:441–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McHale D. Applications of pharmacogenomics in drug discovery. In: Cohen N, editor. Pharmacogenomics and personalized medicine. Totowa: Humana Press; 2008. p. 73–87.

    Google Scholar 

  • Morimoto T, Sakuma M, Matsui K, Kuramoto N, Toshiro J, Murakami J, Fukui T, Saito M, Hiraide A, Bates DW. Incidence of adverse drug events and medication errors in Japan: the JADE study. J Gen Intern Med. 2011;26:148–53.

    Article  PubMed  Google Scholar 

  • My Cancer Genome. EGFR c.2573 T>G (L858R) mutation in non-small cell lung cancer. n.d. https://www.mycancergenome.org/content/disease/lung-cancer/egfr/5. Accessed 03 May 2016.

  • Nadine C, Theresa F. Challenges, opportunities, and evolving landscapes in pharmacogenomics and personalized medicine. In: Cohen N, editor. Pharmacogenomics and personalized medicine. Totowa: Humana Press; 2008. p. 1–26.

    Google Scholar 

  • Nass SJ, Levit LA, Gostin LO. The value and importance of health information privacy. In: Nass SJ, Levit LA, Gostin LO, editors. Beyond the HIPAA privacy rule: enhancing privacy, improving health through research. Washington DC: National Academies Press (US); 2009.

    Chapter  Google Scholar 

  • Neavin D, Kaddurah-Daouk R, Weinshilboum R. Pharmacometabolomics informs pharmacogenomics. Metabolomics. 2016;12:121.

    Article  PubMed  CAS  Google Scholar 

  • NIH, NIGMS. Pharmacogenomics fact sheet. n.d. http://www.nigms.nih.gov/education/pages/factsheet-pharmacogenomics.aspx. Accessed 20 July 2015.

  • Niu N, Wang L. In vitro human cell line models to predict clinical response to anticancer drugs. Pharmacogenomics. 2015;16:273–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nsiah-Jefferson L. Pharmacogenomics: considerations for communities of color. In: Rothstein MA, editor. Pharmacogenomics social, ethical, and clinical dimensions. Hoboken: Wiley-Liss; 2003. p 26790.

    Google Scholar 

  • O’Connor SK, Michaels N, Ferreri S. Expansion of pharmacogenomics into the community pharmacy: billing considerations. Pharmacogenomics. 2015;16:175–80.

    Article  PubMed  CAS  Google Scholar 

  • Ochoa D, Prieto-Pérez R, Román M, Talegón M, Rivas A, Galicia I, Abad-Santos F, Cabaleiro T. Effect of gender and CYP2C9 and CYP2C8 polymorphisms on the pharmacokinetics of ibuprofen enantiomers. Pharmacogenomics. 2015;16:939–48.

    Article  CAS  PubMed  Google Scholar 

  • Ossorio P, Duster T. Race and genetics: controversies in biomedical, behavioral, and forensic sciences. Am Psychol. 2005;60:11528.

    Google Scholar 

  • Pérez-Ramírez C, Cañadas-Garre M, Jiménez-Varo E, Faus-Dáder MJ, Calleja-Hernández MÁ. MET: a new promising biomarker in non-small-cell lung carcinoma. Pharmacogenomics. 2015;16:631–47.

    Article  PubMed  CAS  Google Scholar 

  • Perry CG, Shuldiner AR. Pharmacogenomics of anti-platelet therapy: how much evidence is enough for clinical implementation? J Hum Genet. 2013;58:339–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peterson-Iyer K. Pharmacogenomics, ethics, and public policy. Kennedy Inst Ethics J. 2008;18:1.

    Article  Google Scholar 

  • PharmGKB. CPIC: Clinical Pharmacogenetics Implementation Consortium. n.d.-a. https://www.pharmgkb.org/page/cpic. Accessed 03 May 2016.

  • PharmGKB. DPWG: Dutch Pharmacogenetics Working Group. n.d.-b. https://www.pharmgkb.org/page/dpwg. Accessed 03 May 2016.

  • PharmGKB. Drug labels. n.d.-c. https://www.pharmgkb.org/view/drug-labels.do. Accessed 21 July 2015.

  • Pulley JM, Denny JC, Peterson JF, Bernard GR, Vnencak-Jones CL, Ramirez AH, Delaney JT, Bowton E, Brothers K, Johnson K, Crawford DC, Schildcrout J, Masys DR, Dilks HH, Wilke RA, Clayton EW, Shultz E, Laposata M, McPherson J, Jirjis JN, Roden DM. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther. 2012;92:87–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao US, Mayhew SL, Rao PS. Strategies for implementation of an effective pharmacogenomics program in pharmacy education. Pharmacogenomics. 2015;16:905–11.

    Article  CAS  PubMed  Google Scholar 

  • Reiss SM, American Pharmacists Association. Integrating pharmacogenomics into pharmacy practice via medication therapy management. J Am Pharm Assoc (2003). 2011;51:e64–74.

    Article  Google Scholar 

  • Romualdi C, Balding D, Nasidze IS, Risch G, Robichaux M, Sherry ST, Stoneking M, Batzer MA, Barbujani G. Patterns of human diversity, within and among continents, inferred from biallelic DNA polymorphisms. Genome Res. 2002;12:602–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross CJ, Katzov H, Carleton B, Hayden MR. Pharmacogenomics and its implications for autoimmune disease. J Autoimmun. 2007;28:122–8.

    Article  CAS  PubMed  Google Scholar 

  • Sánchez-Lázaro I, Herrero MJ, Jordán-De Luna C, Bosó V, Almenar L, Rojas L, Martínez-Dolz L, Megías-Vericat JE, Sendra L, Miguel A, Poveda JL, Aliño SF. Association of SNPs with the efficacy and safety of immunosuppressant therapy after heart transplantation. Pharmacogenomics. 2015;16:971–9.

    Article  PubMed  CAS  Google Scholar 

  • Serre D, Pääbo S. Evidence for gradients of human genetic diversity within and among continents. Genome Res. 2004;14:1679–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shabaruddin FH, Fleeman ND, Payne K. Economic evaluations of personalized medicine: existing challenges and current developments. Pharmgenomics Pers Med. 2015;8:115–26.

    PubMed  PubMed Central  Google Scholar 

  • Sharma A, Jacob A, Tandon M, Kumar D. Orphan drug: development trends and strategies. J Pharm Bioallied Sci. 2010;2:290–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sim SC, Kacevska M, Ingelman-Sundberg M. Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects. Pharmacogenomics J. 2013;13:1–11.

    Article  CAS  PubMed  Google Scholar 

  • Singh D. Ethical issues of pharmacogenetics must be addressed, says Nuffield Council. BMJ. 2003;327:701.

    Article  PubMed  PubMed Central  Google Scholar 

  • Soldin OP, Chung SH, Mattison DR. Sex differences in drug disposition. J Biomed Biotechnol. 2011;2011:187103. doi:10.1155/2011/187103.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stjepanovic N, Bedard PL. Elucidating the genomic landscape of breast cancer: how will this affect treatment? Pharmacogenomics. 2015;16:569–72.

    Article  CAS  PubMed  Google Scholar 

  • Sun H, Qu Q, Qu J, Lou XY, Peng Y, Zeng Y, Wang G. URAT1 gene polymorphisms influence uricosuric action of losartan in hypertensive patients with hyperuricemia. Pharmacogenomics. 2015;16:855–63.

    Article  CAS  PubMed  Google Scholar 

  • Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, Rongen GA, van Schaik RH, Schalekamp T, Touw DJ, van der Weide J, Wilffert B, Deneer VH, Guchelaar HJ. Pharmacogenetics: from bench to byte--an update of guidelines. Clin Pharmacol Ther. 2011;89:662–73.

    Article  CAS  PubMed  Google Scholar 

  • Tkáč I, Gotthardová I. Pharmacogenetic aspects of the treatment of Type 2 diabetes with the incretin effect enhancers. Pharmacogenomics. 2016;17:795–804.

    Article  PubMed  CAS  Google Scholar 

  • U.S. FDA. Table of pharmacogenomic biomarkers in drug labeling. n.d. http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm. Accessed 21 July 2015.

  • Ubaldi M, Ricciardelli E, Pasqualini L, Sannino G, Soverchia L, Ruggeri B, Falcinelli S, Renzi A, Ludka C, Ciccocioppo R, Hardiman G. Biomarkers of hippocampal gene expression in a mouse restraint chronic stress model. Pharmacogenomics. 2015;16:471–82.

    Article  CAS  PubMed  Google Scholar 

  • Veenstra DL, Roth JA, Garrison Jr LP, Ramsey SD, Burke W. A formal risk benefit framework for genomic tests: facilitating the appropriate translation of genomics into clinical practice. Genitourin Med. 2010;12:686–93.

    Article  Google Scholar 

  • Ventola CL. The role of pharmacogenomic biomarkers in predicting and improving drug response: part 2: challenges impeding clinical implementation. PT. 2013;38:624–7.

    Google Scholar 

  • Venton G, Colle J, Mercier C, Fanciullino R, Ciccolini J, Ivanov V, Suchon P, Sebahoun G, Beaufils N, Gabert J, Hadjaj D, Costello R. Eradication of T315I mutation in chronic myeloid leukemia without third-generation tyrosine kinase inhibitor: a case report. Pharmacogenomics. 2015;16:677–9.

    Article  CAS  PubMed  Google Scholar 

  • Verbelen M, Lewis CM. How close are we to a pharmacogenomic test for clozapine-induced agranulocytosis? Pharmacogenomics. 2015;16:915–7.

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Zheng Z, YuW LH, Cui B, Cao F. Polymorphisms of the FAS and FASL genes and risk of breast cancer. Oncol Lett. 2012;3:625–8.

    CAS  PubMed  Google Scholar 

  • Weng L, Ziliak D, Im HK, Gamazon ER, Philips S, Nguyen AT, Desta Z, Skaar TC, Consortium on Breast Cancer Pharmacogenomics (COBRA), Flockhart DA, Huang RS. Genome-wide discovery of genetic variants affecting tamoxifen sensitivity and their clinical and functional validation. Ann Oncol. 2013a;24:1867–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weng L, Zhang L, Peng Y, Huang RS. Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics. 2013b;14:315–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wheeler HE, Dolan ME. Lymphoblastoid cell lines in pharmacogenomic discovery and clinical translation. Pharmacogenomics. 2012;13:55–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012;92:414–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wispelwey B. Clinical implications of pharmacokinetics and pharmacodynamics of fluoroquinolones. Clin Infect Dis. 2005;41(Suppl 2):S127–35.

    Article  CAS  PubMed  Google Scholar 

  • Woo HI, Kim JA, Jung HA, Kim KK, Lee JY, Sun JM, Ahn JS, Park K, Lee SY, Ahn MJ. Correlation of genetic polymorphisms with clinical outcomes in pemetrexed-treated advanced lung adenocarcinoma patients. Pharmacogenomics. 2015;16:383–91.

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Deng Q, He B, et al. The diplotype Fas-1377A/−670G as a genetic marker to predict a lower risk of breast cancer in Chinese women. Tumour Biol. 2014;35:9147–61.

    Article  CAS  PubMed  Google Scholar 

  • Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, Minichiello MJ, Fearnhead P, Yu K, Chatterjee N, Wang Z, Welch R, Staats BJ, Calle EE, Feigelson HS, Thun MJ, Rodriguez C, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Giovannucci E, Willett WC, Cancel-Tassin G, Cussenot O, Valeri A, Andriole GL, Gelmann EP, Tucker M, Gerhard DS, Fraumeni Jr JF, Hoover R, Hunter DJ, Chanock SJ, Thomas G. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007;39:645–9.

    Article  CAS  PubMed  Google Scholar 

  • Yiannakopoulou E. Pharmacogenomics and opioid analgesics: clinical implications. Int J Genet. 2015;2015:1. doi:10.1155/2015/368979.

    Article  Google Scholar 

  • Zembutsu H. Pharmacogenomics toward personalized tamoxifen therapy for breast cancer. Pharmacogenomics. 2015;16:287–96.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Sheng J, Kang S, Fang W, Yan Y, Hu Z, Hong S, Wu X, Qin T, Liang W, Zhang L. Patients with exon 19 deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer: a meta-analysis. PLoS One. 2014;9(9):e107161. doi:10.1371/journal.pone.0107161.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharmacokinet. 2009;48:761–804.

    Article  CAS  PubMed  Google Scholar 

  • Zuo Z, Huang M, Kanfer I, Chow MS, Cho WC. Herb-drug interactions: systematic review, mechanisms, and therapies. Evid Based Complement Alternat Med. 2015;2015:1. doi:10.1155/2015/239150.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biotechnology, Institute of Biosciences and Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, 208024, Uttar Pradesh, India

    Dev Bukhsh Singh

Authors
  1. Dev Bukhsh Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dev Bukhsh Singh .

Editor information

Editors and Affiliations

  1. State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China

    Dong-Qing Wei

  2. Center for Neurosciences, The Feinstein Institute for Medical Research, New York, USA

    Yilong Ma

  3. Department of Molecular Medicine, Hofstra Northwell School of Medicine, New York, USA

    William C.S. Cho

  4. Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, Hong Kong

    Qin Xu

  5. College of Computer Science & Technology, Jilin University, Changchun, Jilin, China

    Fengfeng Zhou

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Shanghai Jiao Tong University Press, Shanghai and Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Singh, D.B. (2017). Pharmacogenomics: Clinical Perspective, Strategies, and Challenges. In: Wei, DQ., Ma, Y., Cho, W., Xu, Q., Zhou, F. (eds) Translational Bioinformatics and Its Application. Translational Medicine Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1045-7_13

Download citation

Publish with us

Policies and ethics

Search

Navigation