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Pharmacogenomics in Thrombosis

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Anticoagulants, Antiplatelets, and Thrombolytics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 663))

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Abstract

Inherited or acquired genetic abnormalities play a major role in thromboembolic complications. The goal of pharmacogenomics is to tailor medications to an individual’s genetic makeup in order to improve the benefit-to-risk ratio. Significant findings have been documented showing the effect of certain genetic variations (e.g., in CYP2C9 and VKORC1) on the dose response to warfarin. Pharmacogenomic and genetic information is crucial to improving the efficacy and safety of pharmacotherapy and for the optimal management of thromboembolic disorders.

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References

  1. Cardiovascular Disease Statistics. American Heart Association, 2009 (Accessed January 13, 2009, at http://www.americanheart.org/presenter.jhtml?identifier=4478).

  2. Pharmacogenomics. Human Genome Project Information, 2008. (Accessed January, 2009, at http://www.ornl.gov/sci/techresources/Human_Genome/medicine/pharma.shtml).

  3. Aspinall, M., and Hamermesh, R. (2007) Realizing the promise of personalized medicine Harv Bus Rev 85, 108–17, 65.

    PubMed  Google Scholar 

  4. Vogel, F. (1959) Moderne Probleme der Humangenetick. Ergebn Inn Med Klinderheilk 12, 52–125.

    Article  Google Scholar 

  5. Sadee, W., and Dai, Z. (2005) Pharmacogenetics/genomics and personalized medicine Hum Mol Genet 14(Spec No. 2), R207–14.

    Article  PubMed  CAS  Google Scholar 

  6. Khoury, M. (2003) Genetics and genomics in practice: the continuum from genetic disease to genetic information in health and disease Genet Med 5, 261–8.

    Article  PubMed  Google Scholar 

  7. Ginsburg, G., Donahue, M., and Newby, L. (2005) Prospects for personalized cardiovascular medicine: the impact of genomics J Am Coll Cardiol 46, 1615–27.

    Article  PubMed  Google Scholar 

  8. Zhang, W., Huang, S., and Dolan, E. (2008) Integrating epigenomics into pharmacogenomic studies. Pharmacogenom Personal Med 1, 7–14.

    Google Scholar 

  9. Momary, K. (2007) Cardiovascular pharmacogenomics J Pharm Prac 2007 20, 265–76.

    Article  Google Scholar 

  10. Cresci, S. (2008) From SNPs to functional studies in cardiovascular pharmacogenomics Methods Mol Biol 448, 379–93.

    Article  PubMed  CAS  Google Scholar 

  11. Warfarin drug label revisions. 2007 (Accessed January 13, 2009, at http://www.ama-assn.org/ama1/pub/upload/mm/464/warfarin_label_revis.pdf).

  12. Collins, F.S. (1992) Positional cloning: let’s not call it reverse anymore Nat Genet 1, 3–6.

    Article  PubMed  CAS  Google Scholar 

  13. Drazen, J.M., Yandava, C.N., Dube, L., Szczerback, N., Hippensteel, R., Pillari, A., Israel, E., Schork, N., Silverman, E.S., Katz, D.A., and Drajesk, J. (1999) Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment Nat Genet 22, 168–70.

    Article  PubMed  CAS  Google Scholar 

  14. Krynetski, E.Y., and Evans, W.E. (1999) Pharmacogenetics as a molecular basis for individualized drug therapy: the thiopurine S-methyltransferase paradigm Pharm Res 16, 342–9.

    Article  PubMed  CAS  Google Scholar 

  15. Evans, W.E., and Relling, M.V. (1999) Pharmacogenomics: translating functional genomics into rational therapeutics Science 286, 487–91.

    Article  PubMed  CAS  Google Scholar 

  16. Sata, F., Sapone, A., Elizondo, G., Stocker, P., Miller, V.P., Zheng, W., Raunio, H., Crespi, C.L., and Gonzalez, F.J. (2000) CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity Clin Pharmacol Ther 67, 48–56.

    Article  PubMed  CAS  Google Scholar 

  17. Sachse, C., Brockmoller, J., Bauer, S., and Roots, I. (1999) Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine Br J Clin Pharmacol 47, 445–9.

    Article  PubMed  CAS  Google Scholar 

  18. Stubbins, M.J., Harries, L.W., Smith, G., Tarbit, M.H., and Wolf, C.R. (1996) Genetic analysis of the human cytochrome P450 CYP2C9 locus Pharmacogenetics 6, 429–39.

    Article  PubMed  CAS  Google Scholar 

  19. Takahashi, H., Kashima, T., Nomoto, S., Iwade, K., Tainaka, H., Shimizu, T., Nomizo, Y., Muramoto, N., Kimura, S., and Echizen, H. (1998) Comparisons between in-vitro and in-vivo metabolism of (S)-warfarin: catalytic activities of cDNA-expressed CYP2C9, its Leu359 variant and their mixture versus unbound clearance in patients with the corresponding CYP2C9 genotypes Pharmacogenetics 8, 365–73.

    Article  PubMed  CAS  Google Scholar 

  20. Aithal, G.P., Day, C.P., Kesteven, P.J., and Daly, A.K. (1999) Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications Lancet 353, 717–9.

    Article  PubMed  CAS  Google Scholar 

  21. Ando, Y., Saka, H., Asai, G., Sugiura, S., Shimokata, K., and Kamataki, T. (1998) UGT1A1 genotypes and glucuronidation of SN-38, the active metabolite of irinotecan Ann Oncol 9, 845–7.

    Article  PubMed  CAS  Google Scholar 

  22. Lu, Z., Zhang, R., Carpenter, J.T., and Diasio, R.B. (1998) Decreased dihydropyrimidine dehydrogenase activity in a population of patients with breast cancer: implication for 5-fluorouracil-based chemotherapy Clin Cancer Res 4, 325–9.

    PubMed  CAS  Google Scholar 

  23. Relling, M.V., Hancock, M.L., Rivera, G.K., Sandlund, J.T., Ribeiro, R.C., Krynetski, E.Y., Pui, C.H., and Evans, W.E. (1999) Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus J Natl Cancer Inst 91, 2001–8.

    Article  PubMed  CAS  Google Scholar 

  24. Hoffmeyer, S., Burk, O., von Richter, O., Arnold, H.P., Brockmoller, J., Johne, A., Cascorbi, I., Gerloff, T., Roots, I., Eichelbaum, M., and Brinkmann, U. (2000) 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 97, 3473–8.

    Article  PubMed  CAS  Google Scholar 

  25. Anderson, J., Horne, B., Stevens, S., Grove, A., Barton, S., Nicholas, Z., Kahn, S., May, H., Samuelson, K., Muhlestein, J., and Carlquist, J. (2007) Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation Circulation 116, 2563–70.

    Article  PubMed  CAS  Google Scholar 

  26. Higashi, M., Veenstra, D., Kondo, L., Wittkowsky, A., Srinouanprachanh, S., Farin, F., and Rettie, A. (2002) Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy JAMA 287, 1690–8.

    Article  PubMed  CAS  Google Scholar 

  27. Sconce, E., Khan, T., Wynne, H., Avery, P., Monkhouse, L., King, B., Wood, P., Kesteven, P., Daly, A.K., and Kamali, F. (2005) The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen Blood 106, 2329–33.

    Article  PubMed  CAS  Google Scholar 

  28. Rieder, M., Reiner, A., Gage, B., Nickerson, D., Eby, C., McLeod, H., Blough, D., Thummel, K., Veenstra, D., and Rettie, A. (2005) Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose N Engl J Med 352, 2285–93.

    Article  PubMed  CAS  Google Scholar 

  29. Amitrano, L., Brancaccio, V., Guardascione, M.A., Margaglione, M., Iannaccone, L., D’Andrea, G., Marmo, R., Ames, P.R., and Balzano, A. (2000) Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis Hepatology 31, 345–8.

    Article  PubMed  CAS  Google Scholar 

  30. Foka, Z.J., Lambropoulos, A.F., Saravelos, H., Karas, G.B., Karavida, A., Agorastos, T., Zournatzi, V., Makris, P.E., Bontis, J., and Kotsis, A. (2000) Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages Hum Reprod 15, 458–62.

    Article  PubMed  CAS  Google Scholar 

  31. Manucci, P.M. (2000) The molecular basis of inherited thrombophilia Vox Sang 78(Suppl 2), 39–45.

    PubMed  CAS  Google Scholar 

  32. Soria, J.M., Almasy, L., Souto, J.C., Tirado, I., Borell, M., Mateo, J., Slifer, S., Stone, W., Blangero, J., and Fontcuberta, J. (2000) Linkage analysis demonstrates that the prothrombin G20210A mutation jointly influences plasma prothrombin levels and risk of thrombosis Blood 95, 2780–5.

    PubMed  CAS  Google Scholar 

  33. Ekberg, H., Svensson, P.J., Simanaitis, M., and Dahlback, B. (2000) Factor V R506Q mutation (activated protein C resistance) is an additional risk factor for early renal graft loss associated with acute vascular rejection Transplantation 69, 1577–81.

    Article  PubMed  CAS  Google Scholar 

  34. Chu, K., Wu, S.M., Stanley, T., Stafford, D.W., and High, K.A. (1996) A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism J Clin Invest 98, 1619–25.

    Article  PubMed  CAS  Google Scholar 

  35. Harbrecht, U., Oldenburg, J., Klein, P., Weber, D., Rockstroh, J., and Hanfland, P. (1998) Increased sensitivity of factor IX to phenprocoumon as a cause of bleeding in a patient with antiphospholipid antibody associated thrombosis J Intern Med 243, 73–7.

    Article  PubMed  CAS  Google Scholar 

  36. Oldenburg, J., Quenzel, E.M., Harbrecht, U., Fregin, A., Kress, W., Muller, C.R., Hertfelder, H.J., Schwaab, R., Brackmann, H.H., and Hanfland, P. (1997) Missense mutations at ALA-10 in the factor IX propeptide: an insignificant variant in normal life but a decisive cause of bleeding during oral anticoagulant therapy Br J Haematol 98, 240–4.

    Article  PubMed  CAS  Google Scholar 

  37. Stanley, T.B., Humphries, J., High, K.A., and Stafford, D.W. (1999) Amino acids responsible for reduced affinities of vitamin K-dependent propeptides for the carboxylase Biochemistry 38, 15681–7.

    Article  PubMed  CAS  Google Scholar 

  38. Bray, P.F. (2000) Platelet glycoprotein polymorphisms as risk factors for thrombosis Curr Opin Hematol 7, 284–9.

    Article  PubMed  CAS  Google Scholar 

  39. Kunicki, T.J., Kritzik, M., Annis, D.S., and Nugent, D.J. (1997) Hereditary variation in platelet integrin alpha 2 beta 1 density is associated with two silent polymorphisms in the alpha 2 gene coding sequence Blood 89, 1939–43.

    PubMed  CAS  Google Scholar 

  40. Reiner, A.P., Kumar, P.N., Schwartz, S.M., Longstreth, W.T., Jr., Pearce, R.M., Rosendaal, F.R., Psaty, B.M., and Siscovick, D.S. (2000) Genetic variants of platelet glycoprotein receptors and risk of stroke in young women Stroke 31, 1628–33.

    Article  PubMed  CAS  Google Scholar 

  41. Santoso, S., Kunicki, T.J., Kroll, H., Haberbosch, W., and Gardemann, A. (1999) Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients Blood 93, 2449–53.

    PubMed  CAS  Google Scholar 

  42. Newman, P.J., Derbes, R.S., and Aster, R.H. (1989) The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing J Clin Invest 83, 1778–81.

    Article  PubMed  CAS  Google Scholar 

  43. Williamson, L.M., Hackett, G., Rennie, J., Palmer, C.R., Maciver, C., Hadfield, R., Hughes, D., Jobson, S., and Ouwehand, W.H. (1998) The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening Blood 92, 2280–7.

    PubMed  CAS  Google Scholar 

  44. Zotz, R.B., Winkelmann, B.R., Nauck, M., Giers, G., Maruhn-Debowski, B., Marz, W., and Scharf, R.E. (1998) Polymorphism of platelet membrane glycoprotein IIIa: human platelet antigen 1b (HPA-1b/PlA2) is an inherited risk factor for premature myocardial infarction in coronary artery disease Thromb Haemost 79, 731–5.

    PubMed  CAS  Google Scholar 

  45. Chasman, D., and Adams, R.M. (2001) Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation J Mol Biol 307, 683–706.

    Article  PubMed  CAS  Google Scholar 

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  1. Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA

    Shaker A. Mousa

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  1. , Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sc, Discovery Drive One, Rensselaer, 12144, New York, USA

    Shaker A. Mousa

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Mousa, S.A. (2010). Pharmacogenomics in Thrombosis. In: Mousa, S. (eds) Anticoagulants, Antiplatelets, and Thrombolytics. Methods in Molecular Biology, vol 663. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-803-4_12

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  • DOI: https://doi.org/10.1007/978-1-60761-803-4_12

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-802-7

  • Online ISBN: 978-1-60761-803-4

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