Personalized Genome, Current Status, and the Future of Pharmacogenomics

  • Rohan Mitra
  • Mohan Lal Gope
  • Rajalakshmi Gope


Adverse drug reactions (ADRs) are one of the most dreadful medical conditions that affect a considerable number of individuals when they are taking single or multiple prescription drugs. Often these adverse reactions can occur with specialized drugs that are used to treat more serious disorders. Seldom ADRs can also occur due to intake of even simpler drugs such as penicillin and aspirin. In spite of volumes of data on ADRs, at present we still go through “one size fits all” model in dealing with prescription drugs. This scenario could change due to the emergence of new ways to overcome or minimize ADRs. Pharmacogenomics is one such ways to overcome many horrors of side effects caused by drugs, including ADRs. Pharmacogenomics is the combination of pharmacy and the patient’s genetic composition which interact in an intricate manner to produce positive as well as negative drug reactions. When positive, it is for the betterment of patients, and when negative it leads to ADRs which oftentimes is fatal. Pharmacogenomics is an emerging field of science which is still in its infancy. Technologies that were developed along with the Human Genome Project (HGP), such as faster DNA sequencing protocols and efficient data handling softwares would help in the rapid advancement of pharmacogenomics in the near future. In addition, the reduced cost to obtain complete sequence of individual genome would provide data on single nucleotide polymorphisms (SNPs) and haplotype map (HapMap). These data would provide pattern of individual genetic variations which could be useful in managing diseases and treating patients effectively. In this chapter we will look at the current status and the future of pharmacogenomics which will aid in the development of personalised care. We will also discuss some of the obstacles that would have to be dealt with in achieving such target.


Human Genome Project Vestibular Schwannomas Human Brain Tumor Vestibular Schwannomas Copy Number Polymorphism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India, for logistic support in the preparation of manuscript. Dr. Mohan L. Gope is a retired Professor.


  1. Adams JU (2008) Pharmacogenomics and personalized medicine. Nat Educ 1:1Google Scholar
  2. Anderson JL, Horne BD, Stevens SM et al (2007) Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation 116:2563–2570PubMedCrossRefGoogle Scholar
  3. Ball MP, Thakuria JV, Zaranek AW et al (2012) A public resource facilitating clinical use of genomes. Proc Natl Acad Sci U S A 109:11920–11927PubMedCentralPubMedCrossRefGoogle Scholar
  4. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265PubMedCrossRefGoogle Scholar
  5. Beutler E (1996) G6PD: population genetics and clinical manifestations. Blood Rev 10:45–52PubMedCrossRefGoogle Scholar
  6. Borobia AM, Lubomirov R, Ramırez E et al (2012) An acenocoumarol dosing algorithm using clinical and pharmacogenetic data in Spanish patients with thromboembolic disease. PLoS One 7:e41360. doi: 10.1371/journal.pone.0041360 PubMedCentralPubMedCrossRefGoogle Scholar
  7. Brackmann DE, Kwartler JA (1990) A review of acoustic tumors: 1983–1988. Am J Otol 11:216–232PubMedGoogle Scholar
  8. Brockmoller J, Kirchheiner J, Meisel C et al (2000) Pharmacogenetic diagnostics of cytochrome P450 polymorphisms in clinical drug development and in drug treatment. Pharmacogenomics 1:125–151PubMedCrossRefGoogle Scholar
  9. Chen PL, Scully P, Shew JY, Wang JYJ, Lee WH (1989) Phosphorylation of the retinoblastoma gene product is modulated during cell cycle and cellular differentiation. Cell 58:1193–1198PubMedCrossRefGoogle Scholar
  10. Clark D (2010) Expecting the worst – a publication from the Uppsala Monitoring Centre. Drug Saf 33:1135–1136CrossRefGoogle Scholar
  11. Collins FS, McKusick VA (2001) Implications of the human genome project for medical science. J Am Med Assoc 285:540–544CrossRefGoogle Scholar
  12. Dayalan AHPP, Keshava R, Mathivanan J et al (2006a) The p53 gene and human vestibular schwannomas. Ann Neurosci 13:77–91CrossRefGoogle Scholar
  13. Dayalan AHPPD, Thomas R, Mathivanan M et al (2006b) The tumor suppressor gene retinoblastoma (RB1) in human vestibular schwannomas. Ann Neurosci 13:113–124CrossRefGoogle Scholar
  14. Dayalan AHPP, Mathivanan J, Keshava R et al (2006c) Age dependent phosphorylation and deregulation of p53 in human vestibular schwannomas. Mol Carcinog 45:38–46PubMedCrossRefGoogle Scholar
  15. Desai AA, Innocenti F, Ratain MJ (2003) Pharmacogenomics: road to anticancer therapeutics nirvana? Oncogene 22:6621–6628PubMedCrossRefGoogle Scholar
  16. Foster MW, Sharp RR (2005) Will investments in biobanks, prospective cohorts, and markers of common patterns of variation benefit other populations of drug response and disease susceptibility gene discovery? Pharmacogenomics J 5:75–80PubMedCrossRefGoogle Scholar
  17. Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892PubMedCrossRefGoogle Scholar
  18. Goldstein DB, Cavalleri GL (2005) Genomics: understanding human diversity. Nature 437:1241–1242PubMedCrossRefGoogle Scholar
  19. Grant SFA (2001) Pharmacogenetics and pharmacogenomics: tailored drug therapy for the 21st century. Trends Pharmacol Sci 22:3–4PubMedCrossRefGoogle Scholar
  20. Guengerich FP (2006) Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J 8:E101–E111PubMedCentralPubMedCrossRefGoogle Scholar
  21. Hainaut P, Weiman KG (2009) 30 years and a long way into p53 research. Lancet Oncol 10:913–919PubMedCrossRefGoogle Scholar
  22. Hanahan D, Weinberg RA (2011) Hallmark of cancer: the next generation. Cell 144:646–674PubMedCrossRefGoogle Scholar
  23. Hillman MA, Wilke RA, Caldwell MD et al (2004) Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype. Pharmacogenetics 14:539–547PubMedCrossRefGoogle Scholar
  24. Hinds DA, Stuve LL, Nilsen GB et al (2005) Whole genome patterns of common DNA variation in three human populations. Science 307:1072–1079PubMedCrossRefGoogle Scholar
  25. Hollinger MA (2003) Introduction to pharmacology. CRC Press, Boca Raton, Florida, USA, ISBN 0-415-28033-8Google Scholar
  26. Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Home Page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Accessed 25 Mar 2010
  27. Ingelman-Sundberg M (2004) Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci 25:193–200PubMedCrossRefGoogle Scholar
  28. International HapMap Consortium (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467:52–58CrossRefGoogle Scholar
  29. Kaye AH, Laws ER Jr (eds) (2001) Brain tumors: an encyclopedic approach, 2nd edn. © Harcourt Publishers Limited, LondonGoogle Scholar
  30. Lagoumintzis G, Poulas K, Patrinos GP (2010) Genetic data bases and their potential in pharmacogenomics. Curr Pharm Des 16:2223–2231Google Scholar
  31. Laing RE, Hess P, Shen Y et al (2011) The role and impact of SNPs in pharmacogenomics and personalized medicine. Curr Drug Metab 12:460–486PubMedCrossRefGoogle Scholar
  32. Lander ES (2011) Initial impact of the sequencing of the human genome. Nature 470:187–197PubMedCrossRefGoogle Scholar
  33. Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279:1200–1205PubMedCrossRefGoogle Scholar
  34. Leitner WW, Ying H, Restifo NP (1999) DNA and RNA based vaccines: principles, progress and prospects. Vaccine 18:765–777PubMedCentralPubMedCrossRefGoogle Scholar
  35. Limdi NA, McGwin G, Goldstein JA et al (2008) Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clin Pharmacol Ther 8(83):212–221Google Scholar
  36. Lindquist M (2008) Vigibase, the WHO global ICSR database system: basic facts. Drug Inf J 42:409–419Google Scholar
  37. Ma Q, Lu AY (2011) Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 63:437–459PubMedCrossRefGoogle Scholar
  38. Martuza RL, Eldridge R (1988) Neurofibromatosis 2 (bilateral acoustic neurofibromatosis). N Eng J Med 318:684–688Google Scholar
  39. Mathivanan J, Rohini K, Gope ML et al (2007a) Altered structure and deregulated expression of the tumor suppressor gene retinoblastoma (RB1) in human brain tumors. Mol Cell Biochem 302:67–77PubMedCrossRefGoogle Scholar
  40. Mathivanan J, Rohini K, Gope ML et al (2007b) Possible role of the tumor suppressor gene retinoblastoma (RB1) in human brain tumor development. Ann Neurosci 14:72–82CrossRefGoogle Scholar
  41. McCarthy JJ, Hilfiker R (2000) The use of single-nucleotide polymorphism maps in pharmacogenomics. Nat Biotechnol 18:505–508PubMedCrossRefGoogle Scholar
  42. Minguez P, Parea L, Diella F et al (2012) Deciphering a global network of functionally associated post-translational modifications. Mol Syst Biol 8:599PubMedCentralPubMedGoogle Scholar
  43. Mitra R, Indira Devi B, Gope ML et al (2012) Sodium Butyrate modulates pRb phosphorylation and induces cell death in human vestibular schwannomas in vitro. Indian J Exp Biol 50:19–27PubMedGoogle Scholar
  44. Nagle H, Nagle N (2005) Pharmacology: an introduction. McGraw Hill, Boston. ISBN 0-07-312275-0Google Scholar
  45. Neil D, Carigie J (2004) The ethics of pharmacogenomics. Monash Bioeth Rev 23:9–20PubMedGoogle Scholar
  46. Peterson-Iyer K (2008) Pharmacogenomics, ethics and public policy. Kennedy Inst Ethics J 18:35–56PubMedCrossRefGoogle Scholar
  47. Piccinin S, Tonin E, Sessa S et al (2012) A “twist box” code of p53 inactivation: twist box:p53 interaction promotes p53 degradation. Cancer Cell 22:404–415PubMedCrossRefGoogle Scholar
  48. Rieder MJ, Reiner AP, Gage BF et al (2005) Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 352:2285–2293PubMedCrossRefGoogle Scholar
  49. Roberts NJ, Vogelstein JT, Parmigiani G et al (2012) The predictive capacity of personal genome sequencing. Sci Transl Med 4:135lr3Google Scholar
  50. Rodon J, Saura C, Dienstmann R et al (2012) Molecular prescreening to select patient population in early clinical trials. Nat Rev Clin Oncol 9:359–366PubMedCrossRefGoogle Scholar
  51. Rohini K, Mathivanan J, Dayalan AHPP et al (2007) Loss of heterozygosity of the p53 gene and deregulated expression of its mRNA and protein in human brain tumors. Mol Cell Biochem 300:101–111PubMedCrossRefGoogle Scholar
  52. Rohini K, Mathivanan J, Gope ML et al (2008) Functional modulation of the p53 gene and its protein in human brain tumors. Ann Neurosci 15:75–86CrossRefGoogle Scholar
  53. Rothstein MA, Epps PG (2001) Ethical and legal implications of pharmacogenomics. Nat Rev Genet 2:228–231PubMedCrossRefGoogle Scholar
  54. Sato Y, Laird M, Yoshida T (2010) Biostatistic tools in pharmacogenomics – advances, challenges, potential. Curr Pharm Des 16:2232–2240PubMedCrossRefGoogle Scholar
  55. Schmitta MW, Kennedya SR, Salka JJ et al (2012) Detection of ultra-rare mutations by next-generation sequencing. Proc Natl Acad Sci U S A 109:14508–14513CrossRefGoogle Scholar
  56. Shastry BS (2006) Pharmacogenetics and the concept of individualized medicine. Pharmacogenomics J 6:16–21PubMedCrossRefGoogle Scholar
  57. Thomas R, Dayalan AHPP, Mathivanan J et al (2005) Altered structure and expression of RB1 gene and increased phosphorylation of pRb in human vestibular schwannomas. Mol Cell Biochem 271:113–121PubMedCrossRefGoogle Scholar
  58. Varela MA, Amos W (2010) Heterogeneous distribution of SNPs in the human genome: microsatellites as predictors of nucleotide diversity and divergence. Genomics 95:151–159PubMedCrossRefGoogle Scholar
  59. Venter JC et al (2001) The sequence of the human genome. Science 291:1304–1351PubMedCrossRefGoogle Scholar
  60. Weber WW (1997) Pharmacogenetics, Oxford University Press, New YorkGoogle Scholar
  61. Weiling F (1991) Historical study: Johann Gregor Mendel 1822–1884. Am J Med Genet 40:1–25, discussion 26PubMedCrossRefGoogle Scholar
  62. Weinberg RA (1991) Tumor suppressor genes. Science 254:1138–1146PubMedCrossRefGoogle Scholar
  63. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81:323–330PubMedCrossRefGoogle Scholar
  64. Weinberg RA (2007) Biology of cancer. Garland Sciences, Taylor & Francis Group, LLC, New York, NY, USAGoogle Scholar
  65. Williams-Jones B, Corrigan OP (2003) Rhetoric or hype. Where’s the ethics in pharmacogenomics. Am J Pharmacogenomics 3:375–383PubMedCrossRefGoogle Scholar
  66. Willcox SM, Himmelstein DU, Woolhandler S (1994) Inappropriate drug prescribing for the community-dwelling elderly. J Am Med Assoc 272:292–296CrossRefGoogle Scholar

Websites on SNPs, SNPs in Cancer, GWAS

  1. American Association for Cancer Research Cancer Concepts Factsheet on SNPsGoogle Scholar
  2. Database of Genotype and Phenotype (dbGaP) located at:
  3. The SNP Consortium LTD – SNP searchGoogle Scholar

Copyright information

© Springer India 2013

Authors and Affiliations

  • Rohan Mitra
    • 1
  • Mohan Lal Gope
    • 2
  • Rajalakshmi Gope
    • 1
  1. 1.Department of Human GeneticsNIMHANSBangaloreIndia
  2. 2.BangaloreIndia

Personalised recommendations