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GENETIC ASPECTS OF BETA1-BLOCKERS TREATMENT FOR PATIENTS WITH HYPERTENSION

Authors: Dudchenko I.O., Prystupa L.N.

Pages: 246-255

Abstract

Introduction. Analysis of scientific studies has revealed the relationship between the T393C polymorphism of GNAS1 gene and Arg389Gly of ADRβ1 gene, and effectiveness of treatment using β1-blockers. However, these results are controversial, which may be due to ethnicity of the studied groups. In Ukraine, the study of T393C polymorphism of GNAS1 gene and its impact on the effectiveness of antihypertensive therapy using β1-blockers were not carried out.

Our aim was to determine the impact T393C polymorphisms of gene GNAS1 and Arg389Gly of ADRβ1 gene on efficiency of treatment using β1-blockers for patients with hypertension.

Materials and methods. The study involved 70 patients with verified diagnosis of hypertension. At baseline, β1‑blockers were appointed for patients at doses: metoprolol – 12.5 mg/kg per day, carvedilol – 25 mg/kg per day, and bisoprolol – 5 mg/kg per day. Efficacy of treatment was determined after 2 weeks by measuring heart rate and blood pressure. Polymorphism of gene was determined by polymerase chain reaction followed by restriction fragment analysis. Statistical analysis of the data was performed using the SPSS Statistics 21.0 program.

Discussion. It is proved that determining of T393C polymorphisms of GNAS1 gene and Arg389Gly of ADRβ1 gene plays an important role for the treatment with β1-blockers, because:

    • in patients with T393T genotype of GNAS1 gene observed higher level of reduction of systolic blood pressure and heart rate, when the treatment by β1-blocker was used, than in patients with C393C genotype;
    • in patients with Arg389Arg and Arg389Gly genotypes of ADRβ1 gene the level of reduction of heart rate and systolic blood pressure, when the treatment by β1‑blocker was used, was higher than in patients with Gly389Gly genotype.
    • in case when T393C or C393C genotypes of GNAS1 gene and Gly389Gly of ADRβ1 gene are combined, application of β1-adrenergic blockers is ineffective, even with its dose adjustment.

Key words: β1-blockers, gene polymorphism, heart rate, blood pressure.

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References

  1. Gong Y, McDonough CW, Wang Z, Hou W, Cooper-DeHoff RM, Langaee TY, Beitelshees AL, Chapman AB, Gums JG, Bailey KR, Boerwinkle E, Turner ST, Johnson JA. Hypertension susceptibility loci and blood pressure response to antihypertensives: results from the pharmacogenomic evaluation of antihypertensive responses study. G. 2012;5(6):686–691. doi: 10.1161/CIRCGENETICS.112.964080
  2. Pacanowski MA, Gong Y, Cooper-DehoffRM, Schork NJ, Shriver MD, LangaeeTY, Pepine CJ, Johnson JA. Bold beta-adrenergetic receptor gene polymorphisms and bold beta-blocker treatment outcomes in hypertension. Clinical Pharmacology and Therapeutics. 2008;84(6):715721.doi:10.1038/clpt.2008.139
  3. Leineweber К, Heusch G. β1- and β2-adrenoceptor polymorphisms and cardiovascular diseases. British Journal of Pharmacology. 2009;158(1):6169. doi:10.1111/j.1476-5381.2009.00187.x
  4. Sofowora GG, Dishy V, Muszkat M, Xie HG, Kim RB, Harris PA, Prasad HC, Byrne DW, Nair UB, Wood AJ, Stein CM. А common bold beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to bold beta-blockade. Clinical Pharmacology and Therapeutics. 2003;73(4):366371.
  5. Liu J, Liu ZQ, Tan ZR, Chen XP, Wang LS, Zhou G, Zhou HH. Gly389Arg polymorphism of bold beta1-adrenergic receptor is associated with the cardiovascular response to metoprolol. Clinical Pharmacology and Therapeutics. 2003;74(4):372379.
  6. Liu J, Liu ZQ, Yu BN, Xu FH, Mo W, ZhouG, Liu YZ, Li Q, Zhou HH. Вold beta1-adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clinical Pharmacology and Therapeutics. 2006;80(1):2332.
  7. Johnson JA, Zineh I, Puckett BJ, McGorraySP, Yarandi HN, Pauly DF. Вold beta1-adrenergic receptor polymorphisms and antihypertensive response to.Clinical Pharmacology and Therapeutics. 2003;74(1):4452.
  8. Amosova KM, Sydorchuk LP, Kushnir OV. [Changes in endothelial function under the influence of combination treatment in patients with hypertension]. Bukovinian Medical Herald. 2010;14(4):36.
  9. Sydorchuk LP. [Cellular immunity of patients with hypertension, polymorphism 5 genes influence treatment]. Ukr Med Almanakh. 2008;11(3):143147.
  10. Sydorchuk LP, Amosova KM. [Indicators echocardiogram and geometric patterns of left ventricular in patients with hypertension based on five genes polymorphism]. Ukrainian Therapeutical J. 2008;2:1320.
  11. Sydorchuk LP. [Justification of antihypertensive treatment in patients with essential arterial hypertension depending on individual pharmacogenetic sensitivity]. Ukrainian Cardiology Journal. 2009;5:3551.
  12. Udovychenko MM. Оsoblyvosti perebigu sertsevoi nedostatnosti u khvorykh na tsukrovui diabet 2-ho typu v zalezhnosti vid polimorfizmu gena beta1-adrenoretheptoriv [Peculiarities of heart failure in patients with diabetes mellitus type 2, depending on the gene polymorphism of beta1-adrenergic receptors]. Kharkiv, 2012. 20 p.
  13. Karlsson J, Lind L, Hallberg P, MichaelssonK, Kurland L, Kahan T, Malmqvist K, Ohman KP, Nystrm F, MelhusClinical Cardiology. 2004;27(6):34750.
  14. Saveleva EG. Klinicheskaia i instrumentalnaia otsenka effektivnosti betaksolola u bolnykh gipertonicheskoi bolezniu [Clinical and instrumental evaluation of betaxolol in patients with essential hypertension: genetic aspects of individual sensitivity]. Moscow, 2007. 116 p.
  15. Maneshina OA. Sostoianie i modifikatsiia kletochnnoi β-adrenoretseptsii i rol polimorfizma genov β-adrenoretseptorov v terapii arterialnoi hipertonii i khronicheskoi serdechnoi nedostatochnosti [State and modification of β-cell adrenoretseptsii role of gene polymorphism and β1-adrenergic receptors in the treatment of hypertension and congestive heart failure]. Moscow, 2006. 27 p.
  16. Maneshina OA, Leonova MV, Belousov YuB, Gogolevskaia IK, Erofeeva SB. [Effect of polymorphism of β1-adrenoceptor Arg389Gly to reduce heart rate in patients with chronic heart failure during treatment with metoprolol CR/XL]. Biomedicina. 2006;3:128129.
  17. Minushkina LO. Geneticheskie factory pri gipertonicheskoy bolezni: sviaz s osobennostiami techeniia, razvitiem oslozhnenii, effektivnostiu terapii [Genetic factors in hypertension: association with features of progression, development of complications, and effectiveness of the therapy]. Moscow, 2008. 288 p.
  18. Beitelshees AL, Zineh I, Yarandi HN, PaulyDF, Johnson JA. Influence of phenotype and pharmacokinetics on beta-blocker drug target pharmacogenetics. The Pharmacogenomics J. 2006;6(3):174–178.
  19. Jia H, Hingorani AD, Sharma P, Hopper R, Dickerson C, Trutwein D, Lloyd DD, Brown MJ. Association of the Gsα gene with essential hypertension and response to β-blockade. Hypertension. 1999;34(1):834.
  20. Nieminen T, Lehtimaki T, Laiho J, Rontu R, Niemela K, Kbi T, Lehtinen R, Viik J, Turjanmaa V, Kahnen M. Effects of polymorphisms in beta1-adrenoceptor and α-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study. J Applied Physiology. 2006;100(2):507–511.