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PHARMACOGENETIC TESTING OPPORTUNITIES IN CARDIOLOGY BASED ON EXOME SEQUENCING

https://doi.org/10.20996/1819-6446-2014-10-6-646-650

Abstract

Aim. To study what cardiac drugs currently have any comments on biomarkers and what information can be obtained by pharmacogenetic testing using data exome sequencing in patients with cardiac diseases.

Material and methods. Exome sequencing in random participant of the ATEROGEN IVANOVO study and bioinformatics analysis of the data were performed. Point mutations were annotated using ANNOVAR program, as well as comparison with a number of specialized databases was done on the basis of user protocols.

Results. 11 cardiac drugs and 7 genes which variants can influence cardiac drug metabolism were analyzed. According to exome sequencing of the participant we did not reveal allelic variants that require dose regime correction and careful efficacy control.

Conclusion. The exome sequencing application is the next step to a wide range of personalized therapy. Future opportunities for improvement of the risk-benefit ratio in each patient are the main purpose of the collection and analysis of pharmacogenetic data.

About the Authors

N. V. Shcherbakova
State Research Center for Preventive Medicine
Russian Federation

Petroverigsky per. 10, Moscow, 101990 Russia



A. I. Ershova
State Research Center for Preventive Medicine
Russian Federation

Petroverigsky per. 10, Moscow, 101990 Russia



A. A. Suvorova
State Research Center for Preventive Medicine
Russian Federation

Petroverigsky per. 10, Moscow, 101990 Russia



E. Y. Hlebus
State Research Center for Preventive Medicine
Russian Federation

Petroverigsky per. 10, Moscow, 101990 Russia



A. N. Meshkov
State Research Center for Preventive Medicine
Russian Federation

Petroverigsky per. 10, Moscow, 101990 Russia



S. A. Boytsov
State Research Center for Preventive Medicine
Russian Federation

Petroverigsky per. 10, Moscow, 101990 Russia



References

1. US Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labels. Available at: http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm. Accessed by 11.11.2014.

2. Shimazawa R., Ikeda M. Differences in pharmacogenomic biomarker information in package inserts from the United States, the United Kingdom and Japan. Journal of Clinical Pharmacy and Therapeutics 2013;

3. Meshkov AN, Boytsov SA, Ershova AI, et al. The ATHEROGEN-IVANOVO trial "Investigation of the specific features of the development and progression of ATHEROsclerosis at various sites, including those with a view to the GENetic and epigenetic cardiovascular risk factors – the ESSE-IVANOVO substudy" – design, bioinformation analysis algorithms, and exome sequencing results in pilot group patients. Profilakticheskaya Meditsina 2013;16(6):11-20. Russian (Мешков А.Н., Бойцов С.А., Ершова А.И., и др. Исследование АТЕРОГЕН-ИВАНОВО. Изучение особенностей развития и прогрессирование атеросклероза различной локализации, в том числе с учетом генетических и эпигенетических факторов сердечно-сосудистого риска – субисследование ЭССЕ-Иваново – дизайн, алгоритмы биоинформационного анализа и результаты секвенирования экзомов пациентов пилотной группы. Профилактическая Медицина 2013;16(6):11-20).

4. Ershova AI, Shcherbakova, NV, Suvorova AA, et al. Differential diagnosis of hereditary syndrome hypocholesterolemia using ekzomnogo sekvenirovaniya. Ration Pharmacother Cardiol 2014; 10 (5): 509-12. Russian (Ершова А.И., Щербакова Н.В., Суворова А.А., и др. Дифференциальная диагностика наследственного синдрома гипохолестеринемии с применением экзомного секвенирования. Рациональная Фармакотерапия в Кардиологии 2014; 10(5): 509-12).

5. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-through put sequencing data. Nucleic Acids Res 2010;38(16):e164.

6. Whirl-Carrillo M., McDonagh E. M., Hebert J. M., et al. Pharmacogenomics Knowledge for Personalized Medicine, Clinical Pharmacology & Therapeutics 2012;92(4):414-7.

7. Frueh F.W., Amur S., Mummaneni P., et al. Pharmacogenomic biomarker information in drug labels approved by the United States Food and Drug Administration: prevalence of related drug use. Pharmacotherapy 2008;28(8):992-8.

8. Evans D.A., Mahgoub A., Sloan T.P., et al. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet 1980;17:102-5.

9. Mahgoub A., Idle J.R., Dring L.G., et al. Polymorphic hydroxylation of Debrisoquine in man. Lancet 1977;2:584-6.

10. U.S. Food and Drug Administration. Guidance for Industry: Pharmacogenomic Data Submissions. March 2005. Available at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126957.pdf. Accessed by 11.11.2014.

11. Johansson I., Lundqvist E., Bertilsson L., et al. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultra rapid metabolism of debrisoquine. Proc NatlAcadSci USA 1993;90:11825-9.

12. Ingelman-Sundberg M. The human genome project and novel aspects of cytochrome P450 research. Toxicol Appl Pharmacol 2005;207:52-6.

13. Pinto N., Dolan E. M. Clinically Relevant Genetic Variations in Drug Metabolizing Enzymes Curr Drug Metab 2011;12(5):487-97.

14. Rudorfer M.V., Lane E.A., Potter W.Z. Interethnic dissociation between debrisoquine and desipramine hydroxylation. J Clin Psychopharmacol 1985;5:89-92.

15. Zhan M., Flaws J.A., Gallicchio L., et al. Profiles of tamoxifen related side effects by race and smoking status in women with breast cancer. Cancer Detect Prev 2007;31:384-90.

16. Caraco Y., Sheller J., Wood A.J. Impact of ethnic origin and quinidine coadministration on codeine's disposition and pharmacodynamic effects. J Pharmacol Exp Ther 1999;290:413-22.

17. Home Page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Available at: http://www.cypalleles.ki.se/.Accessed by11.11.2014.

18. Flockhart D.A. Drug interactions and the cytochrome P450 system. The role of cytochrome P4502C19. Clin Pharmacokinet 1995;29(Suppl 1):45-52.

19. Simon T., Verstuyft C., Mary-Krause M., et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363-75.

20. Shuldiner A.R., O'Connell J.R., Bliden K.P., et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009; 302:849-57.

21. Ellis K.J., Stouffer G.A., McLeod H.L., Lee C.R. Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations. Pharmacogenomics 2009;10:1799- 817.

22. Sibbing D., Koch W., Gebhard D., et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 2010;121:512-8.

23. Geisler T., Schaeffeler E., Dippon J., et al. CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation. Pharmacogenomics 2008;9:1251-9.

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

25. Wadelius M., Chen L.Y., Downes K., et al. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J 2005;5:262-70.

26. Rettie A.E., Tai G. The pharmocogenomics of warfarin: closing in on personalized medicine. Mol Interv 2006;6:223-7.

27. Takeuchi F., McGinnis R., Bourgeois S., et al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet 2009;5:e1000433.

28. Haga S.B., Mills R., Moaddeb J. Pharmacogenetic information for patients on drug labels. Pharmacogenomics and Personalized Medicine 2014;7:297-305.

29. Pennisi E. Genomics. 1000 Genomes Project gives new map of genetic diversity. Science 2010;330:574-5.

30. Conrado D.J., Rogers H.L., Zineh I., Pacanowski M.A. Consistency of drug-drug and gene-drug interaction information in US FDA-approved drug labels. Pharmacogenomics 2013;14(2):215-23.


Review

For citations:


Shcherbakova N.V., Ershova A.I., Suvorova A.A., Hlebus E.Y., Meshkov A.N., Boytsov S.A. PHARMACOGENETIC TESTING OPPORTUNITIES IN CARDIOLOGY BASED ON EXOME SEQUENCING. Rational Pharmacotherapy in Cardiology. 2014;10(6):646-650. (In Russ.) https://doi.org/10.20996/1819-6446-2014-10-6-646-650

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)