Skip to main content
SpringerLink
Log in
Book cover

Chronic Illness Care pp 3–16Cite as

Genetic Contributions and Personalized Medicine

  • Chapter
  • First Online:

Abstract

Chronic diseases can be attributed to lifestyle choices, environmental exposures, and genetics. Genomic alterations can increase the risk of developing a chronic condition, and genetic susceptibility can be exacerbated by lifestyle or environment. Numerous medications are available to treat chronic disorders, and even when adhering to best practices, multiple treatment strategies may exist. Polymorphisms in genes encoding drug-metabolizing enzymes, transporters, and targets can influence drug response; therefore gene-based drug-prescribing strategies may identify medications that are more likely to result in a good response. Pharmacogenomics is the study of how variations in genes encoding pharmacokinetic and pharmacodynamic proteins affect pharmacotherapy outcomes. There is a growing body of evidence demonstrating a correlation between genetic polymorphisms and aberrant efficacy, adverse reactions, and dosage requirements. For certain gene-drug interactions, the evidence is sufficiently strong to warrant clinical implementation. Models are being developed exploring how to integrate genomic medicine into routine clinical practice. Methods are needed to discretely curate genomic alterations in electronic medical records, with dissemination of clinical decision support to remind clinicians of important results. Future studies will need to investigate the impact and cost-effectiveness of implementing personalized medicine into patient care.

This is a preview of subscription content, 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   79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   99.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

References

  1. Sharifi M, Rakhit RD, Humphries SE, Nair D. Cardiovascular risk stratification in familial hypercholesterolaemia. Heart. 2016;102(13):1003–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2007;4(4):214–25.

    Article  CAS  PubMed  Google Scholar 

  3. Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Elborn JS. Cystic fibrosis. Lancet. 2016;388(10059):2519–31.

    Article  CAS  PubMed  Google Scholar 

  5. Cahill TJ, Ashrafian H, Watkins H. Genetic cardiomyopathies causing heart failure. Circ Res. 2013;113(6):660–75.

    Article  CAS  PubMed  Google Scholar 

  6. Li J. Inherited neuropathies. Semin Neurol. 2012;32(3):204–14.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266(5182):66–71.

    Article  CAS  PubMed  Google Scholar 

  8. Cuyvers E, Sleegers K. Genetic variations underlying Alzheimer’s disease: evidence from genome-wide association studies and beyond. Lancet Neurol. 2016;15(8):857–68.

    Article  CAS  PubMed  Google Scholar 

  9. Coleman CI, Limone B, Sobieraj DM, Lee S, Roberts MS, Kaur R, et al. Dosing frequency and medication adherence in chronic disease. J Manag Care Pharm. 2012;18(7):527–39.

    PubMed  Google Scholar 

  10. Loffler C, Drewelow E, Paschka SD, Frankenstein M, Eger J, Jatsch L, et al. Optimizing polypharmacy among elderly hospital patients with chronic diseases – study protocol of the cluster randomized controlled POLITE-RCT trial. Implement Sci. 2014;9:151.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kalow W, Tang BK, Endrenyi L. Hypothesis: comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics. 1998;8(4):283–9.

    Article  CAS  PubMed  Google Scholar 

  12. Evans WE, McLeod HL. Pharmacogenomics – drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–49.

    Article  CAS  PubMed  Google Scholar 

  13. Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. N Engl J Med. 2011;364(12):1144–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Clancy JP, Johnson SG, Yee SW, McDonagh EM, Caudle KE, Klein TE, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clin Pharmacol Ther. 2014;95(6):592–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Davies EC, Green CF, Mottram DR, Pirmohamed M. Adverse drug reactions in hospitals: a narrative review. Curr Drug Saf. 2007;2(1):79–87.

    Article  PubMed  Google Scholar 

  16. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–5.

    Article  CAS  PubMed  Google Scholar 

  17. Finkelstein J, Friedman C, Hripcsak G, Cabrera M. Pharmacogenetic polymorphism as an independent risk factor for frequent hospitalizations in older adults with polypharmacy: a pilot study. Pharmgenomics Pers Med. 2016;9:107–16.

    PubMed  PubMed Central  Google Scholar 

  18. Kalow W. Familial incidence of low pseudocholinesterase level. Lancet. 1956;2:576.

    Article  Google Scholar 

  19. Kalow W. Human pharmacogenomics: the development of a science. Hum Genomics. 2004;1(5):375–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003;348(6):529–37.

    Article  PubMed  Google Scholar 

  21. Hicks JK, Swen JJ, Gaedigk A. Challenges in CYP2D6 phenotype assignment from genotype data: a critical assessment and call for standardization. Curr Drug Metab. 2014;15(2):218–32.

    Article  CAS  PubMed  Google Scholar 

  22. Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 2006;79(1):103–13.

    Article  CAS  PubMed  Google Scholar 

  23. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. 1995;333(18):1171–5.

    Article  CAS  PubMed  Google Scholar 

  24. Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319):1061–73.

    Article  CAS  Google Scholar 

  25. Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467(7311):52–8.

    Article  CAS  PubMed  Google Scholar 

  26. He Y, Hoskins JM, McLeod HL. Copy number variants in pharmacogenetic genes. Trends Mol Med. 2011;17(5):244–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gaedigk A. Complexities of CYP2D6 gene analysis and interpretation. Int Rev Psychiatry. 2013;25(5):534–53.

    Article  PubMed  Google Scholar 

  28. Caudle KE, Dunnenberger HM, Freimuth RR, Peterson JF, Burlison JD, Whirl-Carrillo M, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2017;19(2):215–223. https://doi.org/10.1038/gim.2016.87. Epub 2016 Jul 21.

  29. Cleare A, Pariante CM, Young AH, Anderson IM, Christmas D, Cowen PJ, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015;29(5):459–525.

    Article  CAS  PubMed  Google Scholar 

  30. Qaseem A, Barry MJ, Kansagara D, Clinical Guidelines Committee of the American College of P. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;164(5):350–9.

    Article  PubMed  Google Scholar 

  31. Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the pharmacogenomics research network. Clin Pharmacol Ther. 2011;89(3):464–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature. 2015;526(7573):343–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dunnenberger HM, Crews KR, Hoffman JM, Caudle KE, Broeckel U, Howard SC, et al. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annu Rev Pharmacol Toxicol. 2015;55:89–106.

    Article  CAS  PubMed  Google Scholar 

  34. Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, et al. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst. 1999;91(23):2001–8.

    Article  CAS  PubMed  Google Scholar 

  35. McLeod HL, Siva C. The thiopurine S-methyltransferase gene locus – implications for clinical pharmacogenomics. Pharmacogenomics. 2002;3(1):89–98.

    Article  CAS  PubMed  Google Scholar 

  36. Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011;89(3):387–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361(2):123–34.

    Article  CAS  PubMed  Google Scholar 

  38. Westdorp H, Fennemann FL, Weren RD, Bisseling TM, Ligtenberg MJ, Figdor CG, et al. Opportunities for immunotherapy in microsatellite instable colorectal cancer. Cancer Immunol Immunother. 2016;65(10):1249–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Thorn CF, Marsh S, Carrillo MW, McLeod HL, Klein TE, Altman RB. PharmGKB summary: fluoropyrimidine pathways. Pharmacogenet Genomics. 2011;21(4):237–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013;94(6):640–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ke EE, Wu YL. EGFR as a pharmacological target in EGFR-mutant non-small-cell lung cancer: where do we stand now? Trends Pharmacol Sci. 2016;37(11):887–903.

    Article  CAS  PubMed  Google Scholar 

  42. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169–81.

    Article  CAS  PubMed  Google Scholar 

  43. Redig AJ, Janne PA. Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol. 2015;33(9):975–7.

    Article  CAS  PubMed  Google Scholar 

  44. Hunt PW. HIV and aging: emerging research issues. Curr Opin HIV AIDS. 2014;9(4):302–8.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Samji H, Cescon A, Hogg RS, Modur SP, Althoff KN, Buchacz K, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One. 2013;8(12):e81355.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382(9903):1525–33.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Escaut L, Liotier JY, Albengres E, Cheminot N, Vittecoq D. Abacavir rechallenge has to be avoided in case of hypersensitivity reaction. AIDS. 1999;13(11):1419–20.

    Article  CAS  PubMed  Google Scholar 

  48. Martin MA, Klein TE, Dong BJ, Pirmohamed M, Haas DW, Kroetz DL, et al. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clin Pharmacol Ther. 2012;91(4):734–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hershfield MS, Callaghan JT, Tassaneeyakul W, Mushiroda T, Thorn CF, Klein TE, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93(2):153–8.

    Article  CAS  PubMed  Google Scholar 

  50. Martin AM, Nolan D, Gaudieri S, Almeida CA, Nolan R, James I, et al. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc Natl Acad Sci U S A. 2004;101(12):4180–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359(9308):727–32.

    Article  CAS  PubMed  Google Scholar 

  52. Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002;359(9312):1121–2.

    Article  CAS  PubMed  Google Scholar 

  53. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–79.

    Article  PubMed  Google Scholar 

  54. Lennox JL, Landovitz RJ, Ribaudo HJ, Ofotokun I, Na LH, Godfrey C, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014;161(7):461–71.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008;372(9639):646–55.

    Article  CAS  PubMed  Google Scholar 

  56. Bosma P, Chowdhury JR, Jansen PH. Genetic inheritance of Gilbert’s syndrome. Lancet. 1995;346(8970):314–5.

    Article  CAS  PubMed  Google Scholar 

  57. Lubomirov R, Colombo S, di Iulio J, Ledergerber B, Martinez R, Cavassini M, et al. Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study. J Infect Dis. 2011;203(2):246–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ribaudo HJ, Daar ES, Tierney C, Morse GD, Mollan K, Sax PE, et al. Impact of UGT1A1 Gilbert variant on discontinuation of ritonavir-boosted atazanavir in AIDS Clinical Trials Group Study A5202. J Infect Dis. 2013;207(3):420–5.

    Article  CAS  PubMed  Google Scholar 

  59. Vardhanabhuti S, Ribaudo HJ, Landovitz RJ, Ofotokun I, Lennox JL, Currier JS, et al. Screening for UGT1A1 genotype in study A5257 would have markedly reduced premature discontinuation of atazanavir for hyperbilirubinemia. Open Forum Infect Dis. 2015;2(3):ofv085.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Gammal RS, Court MH, Haidar CE, Iwuchukwu OF, Gaur AH, Alvarellos M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for UGT1A1 and atazanavir prescribing. Clin Pharmacol Ther. 2016;99(4):363–9.

    Article  CAS  PubMed  Google Scholar 

  61. Bandiera S, Billie Bian C, Hoshida Y, Baumert TF, Zeisel MB. Chronic hepatitis C virus infection and pathogenesis of hepatocellular carcinoma. Curr Opin Virol. 2016;20:99–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Easterbrook PJ, Group WHOGD. Who to test and how to test for chronic hepatitis C infection – 2016 WHO testing guidance for low- and middle-income countries. J Hepatol. 2016;65(1 Suppl):S46–66.

    Article  PubMed  Google Scholar 

  63. van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584–93.

    Article  PubMed  Google Scholar 

  64. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358(9286):958–65.

    Article  CAS  PubMed  Google Scholar 

  65. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975–82.

    Article  CAS  PubMed  Google Scholar 

  66. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461(7262):399–401.

    Article  CAS  PubMed  Google Scholar 

  67. Muir AJ, Gong L, Johnson SG, Lee MT, Williams MS, Klein TE, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-alpha-based regimens. Clin Pharmacol Ther. 2014;95(2):141–6.

    Article  CAS  PubMed  Google Scholar 

  68. Pilmis B, Puel A, Lortholary O, Lanternier F. New clinical phenotypes of fungal infections in special hosts. Clin Microbiol Infect. 2016;22(8):681–7.

    Article  CAS  PubMed  Google Scholar 

  69. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327–60.

    Article  CAS  PubMed  Google Scholar 

  70. Owusu Obeng A, Egelund EF, Alsultan A, Peloquin CA, Johnson JA. CYP2C19 polymorphisms and therapeutic drug monitoring of voriconazole: are we ready for clinical implementation of pharmacogenomics? Pharmacotherapy. 2014;34(7):703–18.

    Article  CAS  PubMed  Google Scholar 

  71. Miyakis S, van Hal SJ, Ray J, Marriott D. Voriconazole concentrations and outcome of invasive fungal infections. Clin Microbiol Infect. 2010;16(7):927–33.

    Article  CAS  PubMed  Google Scholar 

  72. Mason NT, Bell GC, Quilitz RE, Greene JN, McLeod HL. Budget impact analysis of CYP2C19-guided voriconazole prophylaxis in AML. J Antimicrob Chemother. 2015;70(11):3124–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Hicks JK, Gonzalez BE, Zembillas AS, Kusick K, Murthy S, Raja S, et al. Invasive Aspergillus infection requiring lobectomy in a CYP2C19 rapid metabolizer with subtherapeutic voriconazole concentrations. Pharmacogenomics. 2016;17(7):663–7.

    Article  CAS  PubMed  Google Scholar 

  74. Hicks JK, Crews KR, Flynn P, Haidar CE, Daniels CC, Yang W, et al. Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes. Pharmacogenomics. 2014;15(8):1065–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289(23):3095–105.

    Article  PubMed  Google Scholar 

  76. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Kessler RC. The costs of depression. Psychiatr Clin North Am. 2012;35(1):1–14.

    Article  PubMed  Google Scholar 

  78. Barak Y, Swartz M, Baruch Y. Venlafaxine or a second SSRI: switching after treatment failure with an SSRI among depressed inpatients: a retrospective analysis. Prog Neuro-Psychopharmacol Biol Psychiatry. 2011;35(7):1744–7.

    Article  CAS  Google Scholar 

  79. Hampton LM, Daubresse M, Chang HY, Alexander GC, Budnitz DS. Emergency department visits by adults for psychiatric medication adverse events. JAMA Psychiat. 2014;71(9):1006–14.

    Article  CAS  Google Scholar 

  80. Kennedy SH, Giacobbe P. Treatment resistant depression – advances in somatic therapies. Ann Clin Psychiatry. 2007;19(4):279–87.

    Article  PubMed  Google Scholar 

  81. Hicks JK, Bishop JR, Sangkuhl K, Muller DJ, Ji Y, Leckband SG, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hicks JK, Swen JJ, Thorn CF, Sangkuhl K, Kharasch ED, Ellingrod VL, et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther. 2013;93(5):402–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Altar CA, Carhart JM, Allen JD, Hall-Flavin DK, Dechairo BM, Winner JG. Clinical validity: combinatorial pharmacogenomics predicts antidepressant responses and healthcare utilizations better than single gene phenotypes. Pharmacogenomics J. 2015;15(5):443–51.

    Article  CAS  PubMed  Google Scholar 

  84. Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA, et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 2013;23(10):535–48.

    Article  CAS  PubMed  Google Scholar 

  85. Winner JG, Carhart JM, Altar CA, Goldfarb S, Allen JD, Lavezzari G, et al. Combinatorial pharmacogenomic guidance for psychiatric medications reduces overall pharmacy costs in a 1 year prospective evaluation. Curr Med Res Opin. 2015;31(9):1633–43.

    Article  PubMed  Google Scholar 

  86. Thompson C, Steven PH, Catriona H. Psychiatrist attitudes towards pharmacogenetic testing, direct-to-consumer genetic testing, and integrating genetic counseling into psychiatric patient care. Psychiatry Res. 2015;226(1):68–72.

    Article  PubMed  Google Scholar 

  87. Walden LM, Brandl EJ, Changasi A, Sturgess JE, Soibel A, Notario JF, et al. Physicians’ opinions following pharmacogenetic testing for psychotropic medication. Psychiatry Res. 2015;229(3):913–8.

    Article  PubMed  Google Scholar 

  88. de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics. 2006;47(1):75–85.

    Article  PubMed  Google Scholar 

  89. Lohoff FW, Aquino TD, Narasimhan S, Multani PK, Etemad B, Rickels K. Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics J. 2013;13(1):21–6.

    Article  CAS  PubMed  Google Scholar 

  90. Wilkie MJ, Smith G, Day RK, Matthews K, Smith D, Blackwood D, et al. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. Pharmacogenomics J. 2009;9(1):61–70.

    Article  CAS  PubMed  Google Scholar 

  91. de Leon J, Spina E, Diaz FJ. Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013;35(1):30–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Miranda LF, Gomes KB, Silveira JN, Pianetti GA, Byrro RM, Peles PR, et al. Predictive factors of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer’s disease and mixed dementia: a one-year naturalistic study. J Alzheimers Dis. 2015;45(2):609–20.

    CAS  PubMed  Google Scholar 

  93. Mehanna R, Hunter C, Davidson A, Jimenez-Shahed J, Jankovic J. Analysis of CYP2D6 genotype and response to tetrabenazine. Mov Disord. 2013;28(2):210–5.

    Article  CAS  PubMed  Google Scholar 

  94. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428(6982):486.

    Article  CAS  PubMed  Google Scholar 

  95. Yip VL, Marson AG, Jorgensen AL, Pirmohamed M, Alfirevic A. HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review. Clin Pharmacol Ther. 2012;92(6):757–65.

    Article  CAS  PubMed  Google Scholar 

  96. Chen P, Lin JJ, Lu CS, Ong CT, Hsieh PF, Yang CC, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364(12):1126–33.

    Article  CAS  PubMed  Google Scholar 

  97. Hardt J, Jacobsen C, Goldberg J, Nickel R, Buchwald D. Prevalence of chronic pain in a representative sample in the United States. Pain Med. 2008;9(7):803–12.

    Article  PubMed  Google Scholar 

  98. Sadhasivam S, Chidambaran V. Pharmacogenomics of opioids and perioperative pain management. Pharmacogenomics. 2012;13(15):1719–40.

    Article  CAS  PubMed  Google Scholar 

  99. Ross JR, Rutter D, Welsh K, Joel SP, Goller K, Wells AU, et al. Clinical response to morphine in cancer patients and genetic variation in candidate genes. Pharmacogenomics J. 2005;5(5):324–36.

    Article  CAS  PubMed  Google Scholar 

  100. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240–3.

    Article  CAS  PubMed  Google Scholar 

  101. Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005;14(1):135–43.

    Article  CAS  PubMed  Google Scholar 

  102. Kim H, Neubert JK, San Miguel A, Xu K, Krishnaraju RK, Iadarola MJ, et al. Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament. Pain. 2004;109(3):488–96.

    Article  PubMed  Google Scholar 

  103. Rakvag TT, Ross JR, Sato H, Skorpen F, Kaasa S, Klepstad P. Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol Pain. 2008;4:64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Kirchheiner J, Stormer E, Meisel C, Steinbach N, Roots I, Brockmoller J. Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics. 2003;13(8):473–80.

    Article  CAS  PubMed  Google Scholar 

  105. Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics. 2012;129(5):e1343–7.

    Article  PubMed  Google Scholar 

  106. Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95(4):376–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Chou WY, Yang LC, Lu HF, Ko JY, Wang CH, Lin SH, et al. Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol Scand. 2006;50(7):787–92.

    Article  CAS  PubMed  Google Scholar 

  108. Janicki PK, Schuler G, Francis D, Bohr A, Gordin V, Jarzembowski T, et al. A genetic association study of the functional A118G polymorphism of the human mu-opioid receptor gene in patients with acute and chronic pain. Anesth Analg. 2006;103(4):1011–7.

    Article  CAS  PubMed  Google Scholar 

  109. Mensah GA, Brown DW. An overview of cardiovascular disease burden in the United States. Health Aff (Millwood). 2007;26(1):38–48.

    Article  Google Scholar 

  110. Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med. 1993;328(13):914–21.

    Article  CAS  PubMed  Google Scholar 

  111. Johnson JA, Gong Y, Bailey KR, Cooper-DeHoff RM, Chapman AB, Turner ST, et al. Hydrochlorothiazide and atenolol combination antihypertensive therapy: effects of drug initiation order. Clin Pharmacol Ther. 2009;86(5):533–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Mahmud A, Feely J. Choice of first antihypertensive: simple as ABCD? Am J Hypertens. 2007;20(8):923–7.

    Article  PubMed  Google Scholar 

  113. Schwartz GL, Bailey K, Chapman AB, Boerwinkle E, Turner ST. The role of plasma renin activity, age, and race in selecting effective initial drug therapy for hypertension. Am J Hypertens. 2013;26(8):957–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Dahlberg J, Nilsson LO, von Wowern F, Melander O. Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP. PLoS One. 2007;2(5):e432.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Dahlberg J, Sjogren M, Hedblad B, Engstrom G, Melander O. Genetic variation in NEDD4L, an epithelial sodium channel regulator, is associated with cardiovascular disease and cardiovascular death. J Hypertens. 2014;32(2):294–9.

    Article  CAS  PubMed  Google Scholar 

  116. Luo F, Wang Y, Wang X, Sun K, Zhou X, Hui R. A functional variant of NEDD4L is associated with hypertension, antihypertensive response, and orthostatic hypotension. Hypertension. 2009;54(4):796–801.

    Article  CAS  PubMed  Google Scholar 

  117. Johnson JA, Zineh I, Puckett BJ, McGorray SP, Yarandi HN, Pauly DF. Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003;74(1):44–52.

    Article  CAS  PubMed  Google Scholar 

  118. Liu J, Liu ZQ, Yu BN, Xu FH, Mo W, Zhou G, et al. Beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clin Pharmacol Ther. 2006;80(1):23–32.

    Article  CAS  PubMed  Google Scholar 

  119. Wu D, Li G, Deng M, Song W, Huang X, Guo X, et al. Associations between ADRB1 and CYP2D6 gene polymorphisms and the response to beta-blocker therapy in hypertension. J Int Med Res. 2015;43(3):424–34.

    Article  CAS  PubMed  Google Scholar 

  120. Sjouke B, Kusters DM, Kindt I, Besseling J, Defesche JC, Sijbrands EJ, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J. 2015;36(9):560–5.

    Article  PubMed  Google Scholar 

  121. Group SC, Link E, Parish S, Armitage J, Bowman L, Heath S, et al. SLCO1B1 variants and statin-induced myopathy – a genomewide study. N Engl J Med. 2008;359(8):789–99.

    Article  Google Scholar 

  122. Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014;96(4):423–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94(3):317–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet. 1999;353(9154):717–9.

    Article  CAS  PubMed  Google Scholar 

  125. Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, et al. 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. 2008;83(2):312–21.

    Article  CAS  PubMed  Google Scholar 

  126. Limdi NA, Arnett DK, Goldstein JA, Beasley TM, McGwin G, Adler BK, et al. Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans. Pharmacogenomics. 2008;9(5):511–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005;352(22):2285–93.

    Article  CAS  PubMed  Google Scholar 

  128. Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369(24):2283–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Stankov K, Benc D, Draskovic D. Genetic and epigenetic factors in etiology of diabetes mellitus type 1. Pediatrics. 2013;132(6):1112–22.

    Article  PubMed  Google Scholar 

  130. Noble JA, Erlich HA. Genetics of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2(1):a007732.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Morahan G. Insights into type 1 diabetes provided by genetic analyses. Curr Opin Endocrinol Diabetes Obes. 2012;19(4):263–70.

    Article  CAS  PubMed  Google Scholar 

  132. Medici F, Hawa M, Ianari A, Pyke DA, Leslie RD. Concordance rate for type II diabetes mellitus in monozygotic twins: actuarial analysis. Diabetologia. 1999;42(2):146–50.

    Article  CAS  PubMed  Google Scholar 

  133. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, Steinthorsdottir V, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44(9):981–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26(1):76–80.

    Article  CAS  PubMed  Google Scholar 

  135. Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Pharmacogenomics J. 2009;9(4):242–7.

    Article  CAS  PubMed  Google Scholar 

  136. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011;50(2):81–98.

    Article  CAS  PubMed  Google Scholar 

  137. Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, et al. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest. 2007;117(5):1422–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Zhou K, Donnelly LA, Kimber CH, Donnan PT, Doney AS, Leese G, et al. Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study. Diabetes. 2009;58(6):1434–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, et al. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004;350(18):1838–49.

    Article  CAS  PubMed  Google Scholar 

  140. Pearson ER, Starkey BJ, Powell RJ, Gribble FM, Clark PM, Hattersley AT. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003;362(9392):1275–81.

    Article  CAS  PubMed  Google Scholar 

  141. Wilson CJ, de la Haye K, Coveney J, Hughes DL, Hutchinson A, Miller C, et al. Protocol for a randomized controlled trial testing the impact of feedback on familial risk of chronic diseases on family-level intentions to participate in preventive lifestyle behaviors. BMC Public Health. 2016;16:965.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Vassy JL, Donelan K, Hivert MF, Green RC, Grant RW. Genetic susceptibility testing for chronic disease and intention for behavior change in healthy young adults. J Community Genet. 2013;4(2):263–71.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Teng K, DiPiero J, Meese T, Doerr M, Leonard M, Daly T, et al. Cleveland Clinic’s Center for personalized healthcare: setting the stage for value-based care. Pharmacogenomics. 2014;15(5):587–91.

    Article  CAS  PubMed  Google Scholar 

  144. CMS. Centers for medicare & medicaid services EHR incentive programs. [Available from: https://www.cms.gov/Regulations-and-Guidance/Legislation/EHRIncentivePrograms/index.html?redirect=/ehrincentiveprograms.

  145. Hicks JK, Stowe D, Willner MA, Wai M, Daly T, Gordon SM, et al. Implementation of clinical pharmacogenomics within a large health system: from electronic health record decision support to consultation services. Pharmacotherapy. 2016;36(8):940–8.

    Article  CAS  PubMed  Google Scholar 

  146. Hicks JK, Crews KR, Hoffman JM, Kornegay NM, Wilkinson MR, Lorier R, et al. A clinician-driven automated system for integration of pharmacogenetic interpretations into an electronic medical record. Clin Pharmacol Ther. 2012;92(5):563–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Bell GC, Crews KR, Wilkinson MR, Haidar CE, Hicks JK, Baker DK, et al. Development and use of active clinical decision support for preemptive pharmacogenomics. J Am Med Inform Assoc. 2014;21(e1):e93–9.

    Article  PubMed  Google Scholar 

  148. (AC) DaIGITtEACD. Establishing connectivity and pharmacogenomic clinical decision support rules to protect patients carrying HLA-B*57:01 and TPMT Variants2015. Available from: http://iom.nationalacademies.org/~/media/Files/Activity%20Files/Research/GenomicBasedResearch/Action%20Collaboratives/DIGITizE%20Abacavir%20and%20TPMT%20CDS%20Implementation%20Guide%20-%20Final%201_0.pdf?la=en.

  149. Rasmussen-Torvik LJ, Stallings SC, Gordon AS, Almoguera B, Basford MA, Bielinski SJ, et al. Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems. Clin Pharmacol Ther. 2014;96(4):482–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Weitzel KW, Alexander M, Bernhardt BA, Calman N, Carey DJ, Cavallari LH, et al. The IGNITE network: a model for genomic medicine implementation and research. BMC Med Genet. 2016;9(1):1.

    Google Scholar 

  151. Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, et al. Pharmacogenetics: from bench to byte – an update of guidelines. Clin Pharmacol Ther. 2011;89(5):662–73.

    Article  CAS  PubMed  Google Scholar 

  152. Hoffman JM, Dunnenberger HM, Kevin Hicks J, Caudle KE, Whirl Carrillo M, Freimuth RR, et al. Developing knowledge resources to support precision medicine: principles from the Clinical Pharmacogenetics Implementation Consortium (CPIC). J Am Med Inform Assoc. 2016;23(4):796–801.

    Article  PubMed  Google Scholar 

  153. Dunnenberger HM, Biszewski M, Bell GC, Sereika A, May H, Johnson SG, et al. Implementation of a multidisciplinary pharmacogenomics clinic in a community health system. Am J Health Syst Pharm. 2016;73(23):1956–66.

    Article  PubMed  Google Scholar 

  154. Leckband SG, Kelsoe JR, Dunnenberger HM, George AL Jr, Tran E, Berger R, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther. 2013;94(3):324–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011;90(4):625–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Nagai R, Ohara M, Cavallari LH, Drozda K, Patel SR, Nutescu EA, et al. Factors influencing pharmacokinetics of warfarin in African-Americans: implications for pharmacogenetic dosing algorithms. Pharmacogenomics. 2015;16(3):217–25.

    Article  CAS  PubMed  Google Scholar 

Websites of Importance

Download references

Author information

Authors and Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, Department of Individualized Cancer Management, DeBartolo Family Personalized Medicine Institute, Tampa, FL, USA

    J. Kevin Hicks

  2. Center for Personalized Medicine, NorthShore University HealthSystem, Evanston, IL, USA

    Henry M. Dunnenberger

Authors
  1. J. Kevin Hicks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry M. Dunnenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Kevin Hicks .

Editor information

Editors and Affiliations

  1. Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Timothy P. Daaleman

  2. Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Margaret R. Helton

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hicks, J.K., Dunnenberger, H.M. (2018). Genetic Contributions and Personalized Medicine. In: Daaleman, T., Helton, M. (eds) Chronic Illness Care. Springer, Cham. https://doi.org/10.1007/978-3-319-71812-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-71812-5_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-71811-8

  • Online ISBN: 978-3-319-71812-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation