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Advances in pharmacogenomic research and development

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Abstract

Technological achievements in the last 5 to 10 yr and their application to sequencing and polymorphism discovery in the human genome have fostered a renewed interest in the genetic basis of drug response. Consequently, the field of pharmacogenetics/pharmacogenomics has been gaining momentum, fueled not only on technology but also on results of empirical studies of the human genome and on genetic epidemiology studies of real drugs in patient populations. This review discusses some of the recent advances in pharmacogenomic research and development over the last few years that include understanding the architecture of the human genome, the creation of population deoxyribonucleic acid (DNA)/data banks, assessment of the clinical validity of genetic markers, and experience with regulatory aspects of pharmacogenomics.

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References

  1. Hirschhorn, J. N., Lohmueller, K., Byrne, E., and Hirschhorn, K. A. (2002) Comprehensive review of genetic association studies. Genet. Med. 4, 45–61.

    Article  PubMed  CAS  Google Scholar 

  2. Brower, V. (1998) Genome II: the next frontier. Nat. Biotechnol. 16, 1004.

    Article  PubMed  CAS  Google Scholar 

  3. Marshall, E. (1999) Drug firms to create public database of genetic mutations. Science 284, 406–407.

    Article  PubMed  CAS  Google Scholar 

  4. McCarthy, J. J. and Hilfiker, R. (2000) The use of single-nucleotide polymorphism maps in pharmacogenomics. Nat. Biotechnol. 18, 505–508.

    Article  PubMed  CAS  Google Scholar 

  5. Chin, K. V. and Kong, A. N. (2002) Application of DNA microarrays in pharmacogenomics and toxicogenomics. Pharm. Res. 19, 1773–1778.

    Article  PubMed  CAS  Google Scholar 

  6. Lander, E. S., Linton, L. M., Birren, B., et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921.

    Article  PubMed  CAS  Google Scholar 

  7. Cargill, M., Altshuler, D., Ireland, J., et al. (1999) Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat. Genet. 22, 231–238.

    Article  PubMed  CAS  Google Scholar 

  8. Loots, G. G., Locksley, R. M., Blankespoor, C. M., et al. (2000) Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288, 136–140.

    Article  PubMed  CAS  Google Scholar 

  9. Gabriel, S. B., Schaffner, S. F., Nguyen, H., et al. (2002) The structure of haplotype blocks in the human genome. Science 296, 2225–2229.

    Article  PubMed  CAS  Google Scholar 

  10. Drysdale, C. M., McGraw, D. W., Stack, C. B., et al. (2000) Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 97, 10,483–10,488.

    Article  CAS  Google Scholar 

  11. Lavori, P. W., Krause-Steinrauf, H., Brophy, M., et al. (2002) Principles, organization, and operation of a DNA bank for clinical trials: a Department of Veterans Affairs cooperative study. Control. Clin. Trials. 23, 222–239.

    Article  PubMed  Google Scholar 

  12. Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., and Hirschhorn, J. N. (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat. Genet. 33, 177–182.

    Article  PubMed  CAS  Google Scholar 

  13. Wacholder, S., Rothman, N., and Caporaso, N. (2000) Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias. J. Natl. Cancer Inst. 92, 1151–1158.

    Article  PubMed  CAS  Google Scholar 

  14. Pritchard, J. K. and Rosenberg, N. A. (1999) Use of unlinked genetic markers to detect population stratification in association studies. Am. J. Hum. Genet. 65, 220–228.

    Article  PubMed  CAS  Google Scholar 

  15. Reich, D. E. and Goldstein, D. B. (2001) Detecting association in a case-control study while correcting for population stratification. Genet. Epidemiol. 20, 4–16.

    Article  PubMed  CAS  Google Scholar 

  16. Arranz, M. J., Munro, J., Sham, P., et al. (1998) Metanalysis of studies on genetic variation in 5-HT2A receptors and clozapine response. Schizophr. Res. 32, 93–99.

    Article  PubMed  CAS  Google Scholar 

  17. Ioannidis, J. P., Trikalinos, T. A., Ntzani, E. E., and Contopoulos-Ioannidis, D. G. (2003) Genetic associations in large versus small studies: an empirical assessment. Lancet 361, 567–571.

    Article  PubMed  Google Scholar 

  18. Ioannidis, J. P., Rosenberg, P. S., Goedert, J. J., and O’Brien, T. R. (2002) Commentary: meta-analysis of individual participants’ data in genetic epidemiology. Am. J. Epidemiol. 156, 204–210.

    Article  PubMed  Google Scholar 

  19. McCusker, S. M., Curran, M. D., Dynan, K. B., et al. (2001) Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer’s disease and vascular dementia: a case-control study. Lancet. 357, 436–439.

    Article  PubMed  CAS  Google Scholar 

  20. Arranz, M. J., Munro, J., Birkett, J., et al. (2000) Pharmacogenetic prediction of clozapine response. Lancet. 355, 1615–1616.

    Article  PubMed  CAS  Google Scholar 

  21. Lesko, L. J. and Woodcock, J. (2002) Pharmacogenomic-guided drug development: regulatory perspective. Pharmacogenomics J. 21, 20–24.

    Article  Google Scholar 

  22. Testing DoHaHSSsACoG. (2002) Fed. Regist. 65, 77,631.

  23. Hodgson, J. (2000) First genetic trust banks on genes. Nat. Biotechnol. 18, 1236.

    Article  PubMed  CAS  Google Scholar 

  24. Secretary’s Advisory Committee on Genetics HaS. Available at http://www4.od.nih.gov/oba/sacghs.htm. Accessed on November 23, 2002.

  25. Arranz, M., Collier, D., Sodhi, M., et al. (1995) Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet 346, 281–282.

    Article  PubMed  CAS  Google Scholar 

  26. Malhotra, A. K., Goldman, D., Ozaki, N., Breier, A., Buchanan, R., and Pickar, D. (1996) Lack of association between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine. Am. J. Psychiatry 153, 1092–1094.

    PubMed  CAS  Google Scholar 

  27. Masellis, M., Paterson, A. D., Badri, F., et al. (1995) Genetic variation of 5-HT2A receptor and response to clozapine. Lancet 346, 1108.

    Article  PubMed  CAS  Google Scholar 

  28. Nothen, M. M., Rietschel, M., Erdmann, J., et al. (1995) Genetic variation of the 5-HT2A receptor and response to clozapine. Lancet 346, 908–909.

    Article  PubMed  CAS  Google Scholar 

  29. Nimgaonkar, V. L., Zhang, X. R., Brar, J. S., DeLeo, M., and Ganguli, R. (1996) 5-HT2 receptor gene locus: association with schizophrenia or treatment response not detected. Psychiatr. Genet. 6, 23–27.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jeanette J. McCarthy.

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McCarthy, J.J. Advances in pharmacogenomic research and development. Mol Biotechnol 25, 275–281 (2003). https://doi.org/10.1385/MB:25:3:275

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