Pharmacogenomics: Applications in Drug Discovery and Pharmacotherapy

Hitesh Chopra, Sandeep Kumar, Vandana and Sandeep Arora

  • Download PDF
  • DOI Number

Pharmacogenomics, personalized medicine, DNA Microarray.


Pharmacogenomics is the scientific study which explains individual variability of drug targets and to explore the genetic basis for such changes. With the completion of human genomic study, clear relation could now be established between the drug response in relation to a person\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s genome. Pharmacogenomics, also known as personalized medicine, uses the person\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s genome to determine the dose and dosage regimen, so that therapy could be optimized. As with the techniques like DNA microarray technologies person\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s response to a therapy can be predicted and new therapies could be assigned. In the present review, the current technologies, and past significance has been discussed.

  • Akagah, B., Lormier, A, T., Fournet, A. & Figadere, B., (2008), ‘Oxidation of antiparasitic 2-substituted quinolines using metalloporphyrin catalysts: scale-up of a biomimetic reaction for metabolite production of drug candidates’. Organic and Biomolecular Chemistry, 6, 4494–4497. DOI: 10.1039/b815963g.
  • Alfirevic, A., Jorgensen, A. L., & Williamson, P. R., (2006), HLA-B locus in caucasian patients with carbonize hypersensitivity. Journal of Pharmacogenomics, 7(6), 813-818. PMID:16981842
  • Barkur, S., (2006). Pharmacogenomics and hope for individualized medicine. Asia Pacific Biotech News, 10, 18-19.
  • Chakravarti, A. (2001). To a future of genetic medicine. Nature, 409(6822), 822–823. DOI:10.1038/35057281
  • Cheok, M., H., Pottier, N. & Kager, L. (2009). Pharmacogenetics in acute lymphoblastic leukaemia. Journal of Thrombosis and Haemostasis 46, 39–51. doi: 10.1053/j.seminhematol.2008.09.002
  • Craig, J. (2001). The Sequence of the Human Genome. Science, 291, 1304-1350. DOI: 10.1126/science.1058040.
  • Derisi, J., Penland, L., Brown, P. O., Bittner, M. L., Meltzer, P. S. & Ray, M., (1996). Use of cDNA microarray to analyse gene expression patterns in human cancer. Nature Genetics,14, 457–460.DOI:10.1038/ng1296-457.
  • Ensom, M. H., Chang, T. K., & Patel, P., (2001). Pharmacogenetics the therapeutic drug monitoring of future. Clinical Pharmacokinetics, 40, 783–802. DOI:10.2165/00003088-200140110-00001
  • Eric, S., (2001). Initial sequencing and analysis of human genome. Nature, 409, 860-921. DOI:10.1038/35057062.
  • Evans, W. & Johnson, J. A., (2001). Pharmacogenomics: inherited basis for inter-individual differences in drug response. Annual Review of Genomics and Human Genetics, 2, 9-39.DOI: 10.1146/annurev.genom.2.1.9.
  • Gage, B. F., & Lesko, L. J., (2007). The pharmacogenetics of warfarin: regulatory, scientific and clinical issues. Journal of Thrombosis and Thrombolysis, 25(1), 45-51. DOI: 10.1007/s11239-007-0104-y.
  • Grunstein, M., & Hogness, D. S. (1975). Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proceedings of National Academy of Sciences of United States of America, 72, 3961–3965.
  • Guengerich, F. P. (2001). Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chemical Research in Toxicology, 14, 611–650. DOI: 10.1021/tx0002583.
  • Hung, S.I., Chung, W. H. & Jee, S. H., (2006). Genetic susceptibility to carbamazepine induced cutaneous adverse drug reactions. Pharmacogenet Genomics, 16, 4, 297-306.
  • Iizuka, N., Oka, M. Yamamoto, K., Tangoku, A., Miyamoto, K. & Miyamoto, T., et al., (2003). Identification of common or distinct genes related to antitumor activities of a medicinal herb and its major component by oligonucleotide microarray. International Journal of Cancer, 107,666–672. DOI:10.1002/ijc.11452.
  • Kamatani, Y. K., Matsuda, Y. & Okada, M., (2010). Genome-wide association study of haematological and biochemical traits in Japanese population. Nature Genetics, 42, 210-215. DOI: 10.1016/j.gde.2013.02.006.
  • Kleyn, P.W. & Vesell, E. S., (1998). Genetic variation as a guide to drug development. Science, 281, 1820-1821. DOI: 10.1126/science.281.5384.1820.
  • Lockhart, D. J., Dong, H., Byrne, M. C., Follettie, M. T., Gallo, M. V. & Chee, M. S., et al., (1996).Expression monitoring by hybridization to high-density oligonucleotides arrays. Nature Biotechnology, 14, 1675–1680. DOI:10.1038/nbt1296-1675.
  • Lonjou, C., Thomas, L. & Borot, N.,et al., (2006). A marker for Stevens- Johnson syndrome ethnicitymatters. Journal of Pharmacogenomics, 6(4), 265- 268. DOI:10.1038/sj.tpj.6500356.
  • Lundkvist, J., & Jhonsson, B., (2004). Pharmacogenomics of adverse drug reactions. Fundamental and Clinical Pharmacology, 18, 275–280. DOI:10.1111/j.1472-8206.2004.00239.x
  • Man., C. B., Kwan., P. & Baum., L. (2007). Association between HLA-B*1502 allele & antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia, 48(5), 1015-1018. DOI:10.1111/j.1528-1167.2007.01022.x
  • Marton, M. J., Derisi, J. L. & Bennett, H. A., (1998). Drug target validation and identification of secondary drug target effects using DNA microarrays. Nature Medicine, 4, 1293–1301. DOI: 10.1038/3282
  • Na, L., Yongfei, H., Liying, Z., Xi, Y., Yeshi, Y., Fang, L., Yongliang, Z., Qin D, Xin, W., Zhiqi M., & Baoli, Z. (2014). DNA microarray analysis reveals that antibiotic resistance-gene diversity in human gut microbiota is age related. Science Reports, doi:10.1038/srep04302.
  • Nebert, D.W. (1999). Pharmacogenetics and pharmacogenomics: why is this relevant to the clinical geneticist. Clinical Genetics, 56, 247-258. DOI: 10.1034/j.1399-0004.1999.560401.x
  • Paolo, D. A., Danesi, R., & Tacca, D. M., (2004). Pharmacogenetics of neoplastic diseases.
  • Pharmacological Research, 49, 331-342. DOI: 10.1016/j.phrs.2003.05.002
  • Pirmohamed, M. & Back, D. J., (2001). The pharmacogenomics of HIV therapy. The Journal of Pharmacogenomics, 1, 243–253. DOI:10.1038/sj.tpj.6500069
  • Rebsamen, M. C., Desmeules, J., Daali, Y., Chiappe, A., Chabert, J., Dayer, P., Hochstrasser, D & Rossier, M. F., (2009). The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction. Journal of Pharmacogenomics, 9(1), 34-41.DOI: 10.1038/tpj.2008.7.
  • Relling., M. V. & Giacomini, K. M., (2005). The Pharmacological Basis of Therapeutics, Laurence, L.B., John, S. L. and Keith. L. P. Eds. Tata McGrawHill Publishers, India, pp. 93–115.
  • Rettie, A. E. & Tai, G.Y., (2006). Pharmacogenomics of Warfarin: closing in on individual medicine.Molecular Interventions, 6(4), 223–226.
  • Routledge, P. A., Mahony, M. S. & Woodhouse, K.W. (2004). Adverse drug reactions in elderly patients. British Journal of Clinical Pharmacology, 57, 121–126. DOI: 10.1046/j.1365-2125.2003.01875.x
  • Salerno, L. (2004). Pharmacogenomic data: FDA volutantry and required submission guidance.Pharmacogenomics, 5, 503- 505. doi: 10.1517/14622416.5.5.503
  • Saluz, H. P., Javeed, L., Limmon, G. P., Ruryk, A. & Zhihao, W., (2002). Current Science, 83 (7),829-833.
  • Schena, M., Shalon, D., Davis, R. W., & Brown, P. O., (1995). Quantitative monitoring of gene expression patterns with complementary DNA microarray. Science, 270, 467–470. DOI: 10.1126/science.270.5235.467.
  • Schena, M., Shalon, D., Heller, R., Chai, A., Brown, P.O. & Davis, R.W., (1996). Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proceedings of National Academy of Sciences of United States of America, 93, 10614–10619.
  • Schlichting, I., Berendzen, J., & Chu, K., (2000). The catalytic pathway of cytochrome P450 at atomic resolution. Science, 287 (5458), 1615–1622. DOI: 10.1126/science.287.5458.1615
  • Schwarz, U. I., Ritchie, M. D. & Bradford, Y. (2008). Genetic determinants of response to warfarin during initial anticoagulation. The New England Journal of Medicine, 358, 999–1008.DOI: 10.1056/NEJMoa0708078.
  • Shawn, H., (2005). The Significance of UNESCO’s Universal Declaration on the Human Genome & Human Rights, Journal of Law and Technology, 2(1), 18-47. DOI: 10.2966/scrip.020105.20
  • Southern, E. M., (2000). Blotting at 25. Trends in Biochemical Sciences, 25, 585–588. DOI:
  • Tonisson, N., Zernant, J., Kurg, A., Pavel, H., Slavin, G., Roomere, al ., 2002. Evaluating the arrayed primer extension resequencing assay of TP53 tumor suppressor gene. Proceedings of National Academy of Sciences United States of America, 99,5503–5508.
  • Trau, D., Lee, T. M., Lao, A. I., Lenigk, R. & Hsing, I. M., 2002. Genotyping on a complementary metal oxide semiconductor silicon polymerase chain reaction chip with integrated DNA microarray. Analytical Chemistry, 74, 3168–3173. DOI: 10.1021/ac020053u.
  • Tsoi, P.Y., Wu, H.S., Wong, M.S., Chen, S.L., Fong, W.F., Xiao, et al ., 2003. Genotyping and species identification of Fritillaria by DNA chip technology. Acta Pharmaceutica Sinica, 24, 185–190.
  • Ventura, C., 2005. CAM and cell fate targeting: molecular and energetic insights into cell growth and differentiation. Alternative Medicine, 2,277–283. DOI: 10.1093/ecam/neh100.
  • Vogel, F.,(1959). Modern problem der human genetik. Ergebn. Inn. Med. Kinderheilk, 12, 52-60. DOI: 10.1007/978-3-642-94744-5_2
  • Vuorela, P., Leinonen, M., Saikku, P., Tammela, P., Rauha, J. P & Wennberg, T., et al., (2004). Natural products in the process of finding new drug candidates. Current Medicinal Chemistry, 11,1375– 1389. DOI: 10.2174/0929867043365116.
  • Wang, Z., Du, Q., Wang, F., Wang A,et al., (2004). Microarray analysis of gene expression on herbal glycoside recipes improving deficient ability of spatial learning memory in ischemic mice. Journal of Neurochemistry, 88, 1406–1415. DOI: 10.1046/j.1471-4159.2003.02258.x
  • Warude, D., Chavan, P., Joshi, K., Patwardhan, B. 2003. DNA isolation from fresh and dry samples having high acidic tissues. Plant Molecular Biology Report, 21, 1–6. DOI: 10.1007/BF02772600
  • Wermuth, C. G. (2004). Multitargeted drugs: the end of the ‘one-target-one-disease’ philosophy? Drug Discovery Today, 9, 826–827. DOI: 10.1016/S1359-6446(04)03213-1
  • William, E. & Johnson, A. J. (2001). Pharmacogenomics: the inherited basis for inter-individual differences in drug response. Annual Review of Genomics and Human Genetics, 29-39.DOI: 10.1146/annurev.genom.2.1.9.
  • Zhu, Y., Shennan, M. & Reynolds, K. K., (2007). Determination of Warfarin maintenance dose based on VKORC1 (–1639 G>A) and CYP 2C9 genotypes. Clinical Chemistry, 53(7), 1199–1205. DOI: 10.1373/clinchem.2006.078139