Article PDF


arterial hypertension, personalized therapy

Abstract views: 4
PDF Downloads: 14

How to Cite

Khaitovych, M. (2015). PERSONALIZED ANTIHYPERTENSIVE THERAPY. Medical Science of Ukraine (MSU), 10(1-2), 91-98. Retrieved from


Hypertension is a high risk cardiovascular factor. It is well known that only of 25-30 % patients with hypertension could attain an adequate control of blood pressure.

This review article contains literature data and own research results which deals with problems of hypertension pharmacogenetics. It is described up-to-date data of genetic factor impact on pharmacokinetics and pharmacodynamics of various types of antihypertensive drugs.

It is proven reasonable definition of gene polymorphism CYP2D6 and CYP3A4 in patients with aim to prevent adverse effects of lipophilic beta-blockers and dihydropyridine’s derivatives of calcium-channel blocking drugs respectively.

The article points out on sensitivity of thiazide diuretics in patients with DD genotype of ACE and Gly460 genotype of gene α-adducin; high hydrochlorothiazide effectiveness of TT β3 genotype subunits of G-protein gene.

Beta-adrenoreceptor blocking drugs have shown various effectiveness in patients with vary genotypes of 7 exon eNOS and ADRB1 gene, ACE inhibitors - depends on I/D polymorphism of 16 intron of ACE gene, Gly460Trp polymorphism of α-adducin gene, M235T polymorphism of gene angiotensinogen; receptor antagonists to angiotensin II - depends on 16 intron of ACE gene, 344 C/T polymorphism of aldosterone synthase gene, A1166C polymorphism of AGTR1 gene.

Introduction of the principles of evidence-based research into pharmacogenetics studying will allow concluding definitively about effect of candidate-gene polymorphisms and microRNA expression on the efficacy of antihypertensive drugs administration.

Pharmacogenetics-based personalization could improve hypertension pharmacotherapy in patients to maximum safe and effective.

Article PDF


1. Kukes V.G. Personalizirovannaya meditsina v klinicheskoy farmakologii // Biomeditsina. 2010. Vol. 3, No. 1. P. 22-24 [in Russian].
2. Maydannik V.G., Khaytovich N.V., Pavlishin G.A. [et al.]. Rasprostranennost' izbytochnoy massy tela i povyshennogo arterial'nogo davleniya sredi shkol'nikov raznykh regionov Ukrainy // Mezhdunarodnyy zhurnal pediatrii, akusherstva i ginekologii. 2013. Vol. 3, No 1. P. 33-39 [in Russian].
3. Moybenko A.A., Dosenko V.Ye., Maydannik V.G. [et al.]. Deletsionnyy polimorfizm gena angiotenzin-prevrashchayushchego fermenta u detey i podrostkov s arterial'noy gipertenziyey // Pediatriya. 2007. No. 1. P. 24-28 [in Russian].
4. Maidannyk V.H., Khaitovych M.V., Dosenko V.Ie. Sposib likuvannia arterialnoi hipertenzii u pidlitkiv // Pat. 55963 Ukraina, MPK. A61K 31/00. u201010536. Promyslova vlasnist. Ofitsiinyi biuleten. 2010. No. 24 [in Ukrainian].
5. Sydorchuk L.P., Amosova K.M. Obgruntuvannia pryznachennia antyhipertenzyvnoho likuvannia khvorym na esentsialnu arterialnu hipertenziiu zalezhno vid indyvidualnoi farmakohenetychnoi chutlyvosti // Ukrainskyi kardiolohichnyi zhurnal. 2009. No. 10. Mode of access: [in Ukrainian].
6. Sychev D.A. Farmakogeneticheskoye testirovaniye: klinicheskaya interpretatsiya rezul'tatov // Rekomendatsii dlya praktikuyushchikh vrachey. M., 2011. 84 p. [in Russian].
7. Sychev D.A., G.V. Ramenskaya, I.V. Ignat'yev [et al.]. Klinicheskaya farmakogenetika b-adrenoblokatorov // Klinicheskaya meditsina. 2006. No. 3. P. 4-9 [in Russian].
8. Bielinski S.J., J.E. Olson [et al.]. Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-usinggenomic data to individualize treatment protocol // Mayo Clin. Proc. 2014. Vol. 89, No. 1. P. 25-33.
9. Bochud M., Guessous I. Gene-environment interactions of selected pharmacogenes in arterial hypertension // Expert Rev. Clin. Pharmacol. 2012. Vol. 5, No. 6. Р. 677-686.
10. Brodde O.E. Beta1- and beta2-adrenoceptor polymorphisms and cardiovascular diseases // Fundam Clin Pharmacol. 2008. No. 22. Р. 107-125.
11. Brugts J.J., Isaacs A., de Maat M.P. [et al.]. A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals // J. Hypertens. 2011. Vol. 29, No. 3. Р. 509-19.
12. De Geest S., Ruppar T., Berben L. [et al.]. Medication non-adherence as a critical factor in the management of presumed resistant hypertension: a narrative review // EuroIntervention. 2014. Vol. 9, No. 9. Р. 1102-1109.
13. DeGoma E.M., Rivera G., Lilly S.M. [et al.]. Personalized vascular medicine: individualizing drug therapy // Vascular Med. 2011. Vol. 16, No. 5. Р. 391-404.
14. Duarte J.D., Turner S.T., Tran B. [et al.]. Association of chromosome 12 locus with antihypertensive response to hydrochlorothiazide may involve differential YEATS4 expression // Pharmacogenomics J. 2013. Vol. 13, No. 3. Р. 257-263.
15. Filigheddu F., Argiolas G., Degortes S. [et al.]. Haplotypes of the adrenergic system predict the blood pressure response to beta-blockers in women with essential hypertension // Pharmacogenomics. 2010. Vol. 11, No. 3. Р. 319-325.
16. Goncharov S.V., Gurianova V.L., Stroy D.О. [et al.]. Genetic predisposition to essential hypertension in children: analysis of 17 single nucleotide polymorphisms // Fiziol. Zh. 2013. Vol. 59, No. 6. Р. 12-24.
17. Hayden M.R. Pharmacogenomics // Acta Paediatrica. Abstracts from II Excelence in Paediatrics conference. 2010. Vol. 12, No. 2-4. Р. 21.
18. Höcht C., Bertera F.M., Mayer M.A., Taira C.A. Issues in drug metabolism of major antihypertensive drugs: beta-blockers, calcium channel antagonists and angiotensin receptor blockers // Expert Opin Drug Metab. Toxicol. 2010. Vol. 6, No. 2. Р. 199-211.
19. Irvin M.R., Lynch A.I., Kabagambe E.K. [et al.]. Pharmacogenetic association of hypertension candidate genes with fasting glucose in the GenHAT Study // J. Hypertens. 2010. Vol. 28, No. 10. Р. 2076-2083.
20. Johnson J.A. Pharmacogenomics of antihypertensive drugs: past, present and future // Pharmacogenomics. 2010. No. 4. Р. 487-491.
21. Johnson J.A., Liggett S.B. Cardiovascular pharmacogenomics of adrenergic receptor signaling: clinical implications and future directions // Clin Pharmacol Ther. 2011. Vol. 89, No. 3. Р. 366-378.
22. Kamide K., Asayama K., Katsuya T. [et al.]. Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study // Pharmacogenomics. 2013. Vol. 14, No. 14. Р. 1709-1721.
23. Kurland L., Hallberg P., Melhus H. [et al.]. The relationship between the plasma concentration of irbesartan and the antihypertensive response is disclosed by an angiotensin II type 1 receptor polymorphism: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) Trial // Am. J. Hypertens. 2008. Vol. 21, No. 7. Р. 836-839.
24. Lanzani C., Citterio L., Glorioso N. [et al.]. Adducin- and Ouabain-Related Gene Variants Predict the Antihypertensive Activity of Rostafuroxin, Part 2: Clinical Studies // Science Translational Medicine. 2010. Vol. 2, No. 59. Р. 59-87.
25. Li Y., Zhou Y., Yang P. [et al.]. Interaction of ACE and CYP11B2 genes on blood pressure response to hydrochlorothiazide in Han Chinese hypertensive patients // Clin Exp Hypertens. 2011. Vol. 33, No. 3. Р. 141-146.
26. Mahmoudpour S.H., LeusinkM., van der Putten L. [et al.]. Pharmacogenetics of ACE inhibitor-induced angioedema and cough: a systematic review and meta-analysis // Pharmacogenomics. 2013. Vol. 14, No. 3. Р. 249-260.
27. Martin M.M., Buckenberger J.A., Jiang J. [et al.]. The human angiotensin II type 1 receptor +1166 A/C polymorphism attenuates microrna-155 binding // J. Biol. Chem. 2007. No. 282. Р. 24262-24269.
28. Matthes J., Albus C. Improving adherence with medication: a selective literature review based on the example of hypertension treatment // Deutsch Arztebl. Int. 2014. Vol. 111, No. 4. Р. 41-47.
29. Pacanowski M.A., Gong Y., Cooper-Dehoff R.M. [et al.]. Beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension // Clin Pharmacol Ther. 2008. Vol. 84, No. 6. Р. 715-721.
30. Personalized Medicine Coalition. Retrieved 26 April 2014 // Mode of access:
31. Redekop W.K., Mladsi D. The faces of personalized medicine: a framework for understanding its meaning and scope // Value Health. 2013. Vol. 16, No. 6 Suppl. P. 4-9.
32. Sethupathy P., Borel C., Gagnebin M. [et al.]. Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3′ untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes // Am. J. Hum. Genet. 2007. No. 81. Р. 405-413.
33. Srivastava K., Chandra S., Bhatia J. [et al.]. Association of angiotensinogen (M235T) gene polymorphism with blood pressure lowering response to angiotensin converting enzyme inhibitor (Enalapril) // J. Pharm. Pharm. Sci. 2012. Vol. 15, No. 4. Р. 399-406.
34. Suonsyrjä T., Donner K., Hannila-Handelberg T. [et al.]. Common genetic variation of beta1- and beta2-adrenergic receptor and response to four classes of antihypertensive treatment // Pharmacogenet Genomics. 2010. Vol. 20, No. 5. Р. 342-345.
35. Svensson-Farbom P., Wahlstrand B., Almgren P. [et al.]. A functional variant of the NEDD4L gene is associated with beneficial treatment response with beta-blockers and diuretics in hypertensive patients // J. Hypertens. 2011. Vol. 29, No. 2. Р. 388-395.
36. Table of pharmacogenomic biomarkers in drug labels // Mode of access: 083378.htm
37. Tanner R.M., Lynch A.I., Brophy V.H. [et al.]. Pharmacogenetic associations of MMP9 and MMP12 variants with cardiovascular disease in patients with hypertension // PLoS One. 2011. Vol. 6, No. 8. E. 23609.
38. Turner S.T., Bailey K.R., Fridley B.L. [et al.]. Genomic association analysis suggests chromosome 12 locus influencing antihypertensive response to thiazide diuretic // Hypertension. 2008. Vol. 52, No. 2. Р. 359-365.
39. Whitcomb D.C. Going MAD: development of a «matrix academic division» to facilitate translating research to personalized medicine // Acad Med. 2011. Vol. 86, No. 11. Р. 1353-1359.
40. Wilson C.P., McNulty H., Ward M. [et al.]. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial // Hypertension. 2013. Vol. 61, No. 6. Р. 1302-1308.
41. Ya-Feng L., Xiao-Ming Z., Fan L. [et al.]. Angiotensin-Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism and ACE Inhibitor-Related Cough: A Meta-Analysis // PLoS ONE. 2012. Vol. 7, No. 6. E. 37396.
42. Zhou S.F., Di Y.M., Chan E. [et al.]. Clinical pharmacogenetics and potential application in personalized medicine // Curr. Drug Metab. 2008. Vol. 9, No. 8. Р. 738-784.
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.