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Personalized Medicine in the Treatment of Atrial Fibrillation: Myth or Reality?

https://doi.org/10.20996/1819-6446-2019-15-1-90-94

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Abstract

Due to the spectacular progress made in human genomic studies, molecular biology and genetics have become an essential part of modern medicine making it possible to early detect the risk factors and select the personalized treatment. The genetic studies have been widely used in the diagnosis and treatment of arrhythmias. Significant advances in the study of electrophysiological and genetic mechanisms of life-threatening arrhythmias have been achieved through studies of familial conditions with high risk of sudden cardiac death. However, the area of special interest for a practitioner is the identification of mutations associated with atrial fibrillation (AF). The novel methods enable us to study histological, structural, cellular and molecular causes of this arrhythmia. The two main directions of molecular genetic studies of AF are the identification of genetic mutations causing familial atrial fibrillation and the study of different genes polymorphism predisposing to arrhythmia in general population. Gene polymorphism screening helps both identify AF risk factors and predict its evolution from paroxysmal to chronic type. Emerging genetic studies provided explanation for the variable efficacy of antiarrhythmic drugs. It can be assumed that the clinical use of genetic methods will allow accurate and personalized selection of antiarrhythmics. Currently, therapeutic drug monitoring is widely recommended for a number of medications including cytostatics, aminoglycosides, anticonvulsants, and, by some researchers, antiarrhythmic and anticoagulant drugs. Medicine from the very beginning was intended to be personalized, but until recently it was a little more than a myth. The discovery of the human genome makes it possible to choose the most effective treatment with minimal adverse drug reactions for a particular patient.

About the Authors

V. I. Podzolkov
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

MD, PhD, Professor, Head of Chair of Faculty Therapy №2, 

Trubetskaya ul. 8-2, Moscow, 119991 



A. I. Tarzimanova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

MD, PhD, Professor, Chair of Faculty Therapy №2,

Trubetskaya ul. 8-2, Moscow, 119991 



References

1. Degoma E.M., Rivera G., Lilly S.M. et al. Personalized vascular medicine: individualizing drug therapy. Vascular Med. 2011;16(5):391-404. doi:10.1177/1358863X11422251.

2. Hamburg M.A., Collins F.S. The path to personalized medicine. N Engl J Med. 2010;363(4):301-4. doi:10.1056/NEJMp1006304.

3. Dedov I.I., Tyulpakov A.N., Chekhonin V.P. et al. Personalized medicine: State-of-the-art and prospects. Vestn Ross Akad Med Nauk. 2012;(12):4-12. (In Russ).

4. Jain K.K. From molecular diagnostics to personalized medicine. Exp Rev Mol Diagn 2002;2(4):299- 301. doi:10.1586/14737159.2.4.299.

5. Scudellari M. Genomics contest underscores challenges of personalized medicine. Nat Med. 2012;18(3):326. doi:10.1038/nm0312-326.

6. Hoggatt J. Personalized medicine--trends in molecular diagnostics: exponential growth expected in the next ten years. Mol Diagn Ther. 2011;15(1):53-5. doi:10.2165/11534880-000000000-00000.

7. Hodgson D.R., Wellings R., Harbron C. Practical perspectives of personalized health care in oncology. N Biotechnol. 2012;29(6):656-64. doi:10.1016/j.nbt.2012.03.001.

8. McCarthy J.J., McLeod H.L., Ginsburg G.S: Genomic medicine: a decade of successes, challenges, and opportunities. Sci Transl Med. 2013;5:189sr4. doi:10.1126/scitranslmed.3005785.

9. Brugada P., Brugada J. Right bundle branch block, present ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol. 1992;20:1391-6.

10. Roden D.M., Spooner P.M. Inherited long QT syndromes: paradigm for understanding arrhyhmogenesis. J Cardiovasc Electrophys. 1999;10:1664-83.

11. Wang Q., Chen Q., Towbin J.A. Genetics, molecular mechanisms and management of Long QT syndrome. Ann Med. 1998;30:58-65.

12. Guidelines for the management of atrial fibrillation. The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace. 2010;12(10):1360-420. doi:10.1093/europace/euq350.

13. Oslopov V.N., Oslopova Y.V. Twenty year’s search of the «gene of atrium fibrillation». Practical Medicine. 2013;71(3):12-5. (In Russ.).

14. Heijman J. Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circulation Research. 2014;114(9):1483-99. doi:10.1161/CIRCRESAHA. 114.302226.

15. Chen Y-H., Xu S-J., Bendahhou S. et al. KCNQ1 Gain-of-function mutation in familial atrial fibrillation. Science 2003; 299:251-254. doi:10.1126/science.1077771.

16. Olson T.M., Michels V.V., Ballew J.D. et al. Sodium channel mutation sand susceptibility to heart failure and atrial fibrillation. JAMA. 2005;293:491-3. doi:10.1001/jama.293.4.447.

17. Gollob M.H., Jones D.L., Krahn A.D. et al. Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N Engl J Med. 2006;354:2677-88. doi:10.1056/NEJMoa052800.

18. Otway R., Vandenberg J.I., Guo G. et al. Stretch-sensitive KCNQ1 mutation A link between genetic and environmental factors in the pathogenesis of atrial fibrillation? J Am Coll Cardiol. 2007;49:578- 86. doi:10.1016/j.jacc.2006.09.044.

19. Hodgson-Zingman D.M., Karst M.L., Zingman L.V. et al. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation. N Engl J Med. 2008;359:158-65. doi:10.1056/NEJMoa0706300.

20. Olson T.M., Alekseev A.E., Liu X.K. et al. Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum Mol Genet. 2006;15:2185-91. doi:10.1093/hmg/ ddl143.

21. Darbar D., Kannankeril P.J., Donahue B.S. et al. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation. 2008;117:1927-35. doi:10.1161/CIRCULATIONAHA. 107.757955.

22. Zhang X., Chen S., Yoo S. et al. Mutation in nuclear pore component NUP155 leads to atrial fibrillation and early sudden cardiac death. Cell. 2008;135:1017-27. doi:10.1016/j.cell.2008.10.022.

23. Gensini F., Padeletti L., Fatini C. et al. Angiotensin converting enzyme and endothelial nitric oxide synthase polymorphisms in patients with atrial fibrillation. Am J Cardiol. 2003;91:678-683. doi:10.1016/S0002-9149(02)03403-3.

24. Tsai C., Lai L., Chang F. et al. Renin-angiotensin gene polymorphism and atrial fibrillation. Clin Sci. 2004;106:653-9. doi:10.1161/01.CIR.0000124487.36586.26.

25. Burzotta F., Iacoviello L., Di Castelnuovo A. et al. Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am J Cardiol. 2001;88(10):125-8. doi:10.1016/S0002-9149(01)02046-X.

26. Christiansen J., Dyck J.D., Elyas B.G. et al. Chromosome 1q21.1 contiguous gene deletion is associated with congenital heart disease. Circ Res. 2004;94(11):1429-35. doi:10.1161/01. RES.0000130528.72330.5c.

27. McCarthy J.J., McLeod H.L., Ginsburg G.S. Genomic medicine: a decade of successes, challenges, and opportunities. Sci Transl Med. 2013;5:189sr4. doi:10.1126/scitranslmed.3005785.

28. Gudbjartsson D.F., Arnar D.O., Helgadottir A. et al. Variants confer ring risk of atrial fibrillation on chromosome 4q25. Nature. 2007;448:353-7. doi:10.1038/nature06007.

29. Gudbjartsson D.F., Holm H., Gretarsdottir S. et al. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat Genet. 2009;8:876-8. doi:10.1038/ng.417.

30. Benjamin E.J., Rice K.M., Arking D.E. et al. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet. 2009;41:879-81. doi:10.1038/ng.416.

31. Ellinor P.T., Lunetta K.L., Glazer N.L. et al. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet. 2010;42:240-44. doi:10.1038/ng.537.

32. Yayan J. Emerging families of biomarkers for coronary artery disease: inflammatory mediators. Vascular Health and Risk Management. 2013; 9(1):435-456. doi:10.2147/VHRM.S45704.

33. Kolpachkova E.V., Sokolova A.A., Napalkov D.A. Personalized medicine in cardiology: state, problems and prospects. Medical Council. 2017;12:162-8. (In Russ.)

34. Lunshof J.E., Gurwitz D: Pharmacogenomic testing: knowing more, doing better. Clin Pharmacol Ther. 2012;91:387-9. doi:10.1038/clpt.2011.339

35. Parvez B., Vaglio J., Rowan S. et al. Symptomatic response to antiarrhythmic drug therapy is modulated by a common single nucleotide polymorphism in atrial fibrillation. J Am Coll Cardiol. 2012;60(6):539-45. doi: 10.1016/j.jacc.2012.01.070. doi:10.1016/j.jacc.2012.01.070.

36. Kukes V.G., Bochkov N.P., eds. Clinical pharmacogenomics. Moscow: GEOTAR-MEDIA; 2007. 248 p. (/(In Russ.)

37. Roden D.M., Tyndale R.F. Genomic medicine, precision medicine, personalized medicine: what’s in a name? Clin Pharmacol Ther. 2013;94:169-72. doi:10.1038/clpt.2013.101.

38. Sychev D.K., Miheeva Y.A., Kropacheva E.S. et al. Influence of polymorphism CYP2C9 on pharmacokinetics and pharmacodynamics of warfarin in patients with permanent atrial fibrillation. Klin Med. 2007;1:57-60. (In Russ.)

39. Nishiyama M. Personalized medicine and molecular targets of drugs. Nihon Rinsho. 2010;68(10):1917-22.

40. Mirnezami R., Nicholson J., Darzi A. Preparing for precision medicine. N Engl J Med. 2012;366(6):489-91. doi:10.1056/NEJMp1114866.


For citation:


Podzolkov V.I., Tarzimanova A.I. Personalized Medicine in the Treatment of Atrial Fibrillation: Myth or Reality? Rational Pharmacotherapy in Cardiology. 2019;15(1):90-94. (In Russ.) https://doi.org/10.20996/1819-6446-2019-15-1-90-94

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