Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

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234 Applying Pharmacogenomics in Therapeuticscomplex traits, future pharmacogenomic applications would benefit morefrom considering these potential effects. Similarly, future pharmacogenomicapproaches to considering both gene and environmental factors(such as food intake) will be necessary to provide a more comprehensivepicture of the determinants for therapeutic response variation.STUDY QUESTIONS1. Why is drug response a complex trait or phenotype?2. What are the general strategies for pharmacogenomic discovery?3. Which gene is currently the most studied for pharmacogenomics of COPD?4. Why are there overlapping pharmacogenomic loci between COPD andasthma?5. Are there any ongoing clinical trials for pharmacogenetics and pharmacogenomicsin pulmonary hypertension?Answers1. Drug response is likely affected by multiple factors including both geneticand nongenetic factors (e.g., environment, food intake).2. A candidate gene–based approach may be used if there is reasonable priorknowledge. In contrast, an unbiased approach may be used for a genomewidescan for associated loci.3. To date, most studies have been focused on the roles of common geneticvariants in the ADRB2 gene (encoding β2-adrenergic receptor) on bronchodilatorresponsiveness (BDR).4. These two disorders share certain pathogenesis pathways. Many of the therapiesfor asthma are also used for treating COPD.5. Yes, for example, there are the Pharmacogenomics in Pulmonary ArterialHypertension Trial with the goal to determine, clinically, in PAH patientswhether associations exist between the efficacy and toxicity of sitaxsentan,bosentan, and ambrisentan and several gene polymorphisms in severalkey disease- and therapy-specific genes, and the PILGRIM Trial betweenBMPR2 mutations and hemodynamic response by iloprost inhalation.REFERENCES1. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the humangenome. Nature 2001;409:860–921.2. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science2001;291:1304–51.3. Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contributionto complex traits. Nature Reviews 2009;10:241–51.4. Hindorff LA, Sethupathy P, Junkins HA, et al. Potential etiologic and functionalimplications of genome-wide association loci for human diseases and traits.Proceedings of the National Academy of Sciences of the United States of America2009;106:9362–7.
Applying Pharmacogenomics in the Therapeutics of Pulmonary Diseases2355. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulanttherapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: AmericanCollege of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest2012;141:e152S–84S.6. Gardiner SJ, Begg EJ. Pharmacogenetics, drug-metabolizing enzymes, and clinicalpractice. Pharmacological Reviews 2006;58:521–90.7. Reich DE, Cargill M, Bolk S, et al. Linkage disequilibrium in the human genome.Nature 2001;411:199–204.8. Barnes PJ. Chronic obstructive pulmonary disease. The New England Journal ofMedicine 2000;343:269–80.9. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management,and prevention of chronic obstructive pulmonary disease: GOLD executive summary.American Journal of Respiratory and Critical Care Medicine 2007;176:532–55.10. Coxson HO, Dirksen A, Edwards LD, et al. The presence and progression of emphysemain COPD as determined by CT scanning and biomarker expression: A prospectiveanalysis from the ECLIPSE study. The Lancet 2013;1:129–36.11. Kim V, Han MK, Vance GB, et al. The chronic bronchitic phenotype of COPD:An analysis of the COPDGene Study. Chest 2011;140:626–33.12. Kim V, Criner GJ. Chronic bronchitis and chronic obstructive pulmonary disease.American Journal of Respiratory and Critical Care Medicine 2013;187:228–37.13. Corhay JL, Vincken W, Schlesser M, Bossuyt P, Imschoot J. Chronic bronchitis inCOPD patients is associated with increased risk of exacerbations: A cross-sectionalmulticentre study. International Journal of Clinical Practice 2013;67:1294–301.14. van der Molen T, Miravitlles M, Kocks JW. COPD management: Role of symptomassessment in routine clinical practice. International Journal of Chronic ObstructivePulmonary Disease 2013;8:461–71.15. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160sequelae of 289 diseases and injuries 1990–2010: A systematic analysis for the GlobalBurden of Disease Study 2010. The Lancet 2012;380:2163–96.16. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235causes of death for 20 age groups in 1990 and 2010: A systematic analysis for theGlobal Burden of Disease Study 2010. The Lancet 2012;380:2095–128.17. Decramer M, Janssens W, Miravitlles M. Chronic obstructive pulmonary disease.The Lancet 2012;379:1341–51.18. WHO. The global burden of disease: 2004 update. WHO, Geneva, Switzerland; 2008.19. Iribarren C, Tekawa IS, Sidney S, Friedman GD. Effect of cigar smoking on the riskof cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men.The New England Journal of Medicine 1999;340:1773–80.20. Salvi S. Tobacco smoking and environmental risk factors for chronic obstructivepulmonary disease. Clinics in Chest Medicine 2014;35:17–27.21. Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. The Lancet2009;374:733–43.22. Mayer AS, Newman LS. Genetic and environmental modulation of chronic obstructivepulmonary disease. Respiration Physiology 2001;128:3–11.23. Foreman MG, Campos M, Celedon JC. Genes and chronic obstructive pulmonarydisease. The Medical Clinics of North America 2012;96:699–711.24. Brode SK, Ling SC, Chapman KR. Alpha-1 antitrypsin deficiency: A commonly overlookedcause of lung disease. CMAJ 2012;184:1365–71.25. Salpeter SR. Bronchodilators in COPD: Impact of beta-agonists and anticholinergicson severe exacerbations and mortality. International Journal of Chronic ObstructivePulmonary Disease 2007;2:11–18.
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DedicationWe dedicate this book to
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viiiContentsChapter 10 Pharmacogeno
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EditorsXiaodong Feng, PhD, PharmD,
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BIOMEDICAL SCIENCEApplying Pharmaco
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Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

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