Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study

Huda Mohammed Alkreathy, Khlood Mohammed Eid Alsayyid, Jumana Y Alaama, Kamal Al Ghalayini, Shahid Karim, Ahmed Esmat, Zoheir A Damanhouri, Huda Mohammed Alkreathy, Khlood Mohammed Eid Alsayyid, Jumana Y Alaama, Kamal Al Ghalayini, Shahid Karim, Ahmed Esmat, Zoheir A Damanhouri

Abstract

Background: Bisoprolol is an effective β1-adrenergic blocker, an inter-individual genetic variability was recorded in its response. This study aimed at investigating the association of CYP2D6*2A (rs1080985) and CYP2D6*10 (rs1065852) single-nucleotide polymorphism (SNP) with Bisoprolol response in cardiac patients attending King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia.

Patients and methods: In the study, 107 patients were enrolled. Five mL of venous blood was collected from each patient and genotyping for CYP2D6*2A and CYP2D6*10 using Vivid® CYP2D6 Green Screening Kit (Life Technologies, USA). Response to Bisoprolol was evaluated through assessment of diastolic and systolic blood pressure and by measuring Bisoprolol plasma level using triple quad mass spectrometer (TQ-MS).

Results: All patients were found to carry homozygous wild type CYP2D6*10 (GG) and none were carrying heterozygous (GA) or mutant homozygous (AA) genotype. CYP2D6*2A allele was detected in the homozygous wild type (GG) in 70 out of 107 patients, the heterozygous (GC) in 19 patients, and the homozygous mutant (CC) in 18 patients with minor allele frequency (MAF) of 25.7%. The plasma concentrations of Bisoprolol in CC carriers were significantly lower than those in GG & CC carriers by 25%, and 51%; respectively. Higher systolic and diastolic blood pressures were also observed in CC carriers than GG and CC carriers.

Conclusion: There is a possible association of CYP2D6*2A genotype with plasma concentration of bisoprolol. This could provide a helpful tool to choose the optimum dose for bisoprolol, depending on the patient's genotyping, in order to increase effectiveness and ameliorate its toxicity.

Keywords: Bisoprolol; CYP2D6*10; CYP2D6*2A; Genotyping; Hypertension.

© 2020 The Author(s).

Figures

Fig. 1
Fig. 1
Demographic characteristics of enrolled population (n = 107).

References

    1. Albani D., Boneschi F.M., Biella G., Giacalone G., Lupoli S., Clerici F., Benussi L., Ghidoni R., Galimberti D., Squitti R. Replication study to confirm the role of CYP2D6 polymorphism rs1080985 on donepezil efficacy in Alzheimer’s disease patients. J. Alzheimer’s Dis. 2012;30:745–749.
    1. Aldiab A., Shubair M.M., Al-Zahrani J.M., Aldossari K.K., Al-Ghamdi S., Househ M., Razzak H.A., El-Metwally A., Jradi H. Prevalence of hypertension and prehypertension and its associated cardioembolic risk factors; a population based cross-sectional study in Alkharj. Saudi Arabia. BMC Public Health. 2018;18:1327.
    1. Alshaikh M.K., Filippidis F.T., Baldove J.P., Majeed A., Rawaf S. Women in Saudi Arabia and the Prevalence of Cardiovascular Risk Factors: A Systematic Review. Journal of Environmental and Public Health. 2016;2016:1–15. doi: 10.1155/2016/7479357.
    1. Buś-Kwaśnik K., Rudzki P.J., Ksycińska H., Leś A., Serafin-Byczak K., Raszek J., Bielak A., Wybraniec A., Płatek A.E., Szymański F.M. Bioequivalence study of 2.5 mg film-coated bisoprolol tablets in healthy volunteers. Kardiol. Pol. (Polish Hear. Journal) 2017;75:48–54.
    1. Delahaut P., Levaux C., Eloy P., Dubois M. Validation of a method for detecting and quantifying tranquillisers and a β-blocker in pig tissues by liquid chromatography–tandem mass spectrometry. Analytica chimica acta. 2003;483(1–2):335–340.
    1. Dezsi C.A., Szentes V. The real role of β-blockers in daily cardiovascular therapy. Am. J. Cardiovasc. Drugs. 2017;17:361–373.
    1. Kumosani T.A., Alama M.N., Iyer A. Cardiovascular diseases in Saudi Arabia. Prime Res Med. 2011;1:1–6.
    1. Long A.N., Dagogo-Jack S. Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection. J Clin Hypertens (Greenwich). 2011;13:244–251. doi: 10.1111/j.1751-7176.2011.00434.x.
    1. Mahmood D., Jahan K., Habibullah K. Primary prevention with statins in cardiovascular diseases: A Saudi Arabian perspective. J. Saudi Hear. Assoc. 2015;27:179–191.
    1. MOH, 2018. MOH Statistical Yearbook 2018. (accessed 20 February 2020)
    1. Myburgh R., Hochfeld W.E., Dodgen T.M., Ker J., Pepper M.S. Cardiovascular pharmacogenetics. Pharmacol. Ther. 2012;133:280–290.
    1. Nevzorova, V.A., Zakcharchuk, N.V., Nastradin, O.V., Pomogalova, O.G., 2007. Bisoprolol and metformin in patients with arterial hypertension and metabolic syndrome. Rational Pharmacotherapy in Cardiology. 2007;3(5):54-57.
    1. Nozawa T., Taguchi M., Tahara K., Hashimoto Y., Igarashi N., Nonomura M., Kato B., Igawa A., Inoue H. Influence of CYP2D6 genotype on metoprolol plasma concentration and β-adrenergic inhibition during long-term treatment: a comparison with bisoprolol. J. Cardiovasc. Pharmacol. 2005;46:713–720.
    1. Quiel L., Velásquez I.M., Gómez B., Motta J., Herrera-Ballesteros V. Social determinants and cardiovascular disease mortality in Panama, 2012–2016. BMC Public Health. 2019;19:199.
    1. Shin J., Johnson J.A. Pharmacogenetics of β-Blockers. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2007;27:874–887.
    1. Taguchi M., Nozawa T., Igawa A., Inoue H., Takesono C., Tahara K., Hashimoto Y. Pharmacokinetic variability of routinely administered bisoprolol in middle-aged and elderly Japanese patients. Biol. Pharm. Bull. 2005;28:876–881.
    1. Turner R.M., Fontana V., Bayliss M., Whalley S., Castelazo A.S., Pirmohamed M. Development, validation and application of a novel HPLC-MS/MS method for the quantification of atorvastatin, bisoprolol and clopidogrel in a large cardiovascular patient cohort. J. Pharm. Biomed. Anal. 2018;159:272–281.
    1. WHO, 2017. Report on cardiovascular diseases, WHO. (accessed 20 February 2020)
    1. Xiao T., Jiao B., Zhang W., Tang B., Shen L. Effect of the CYP2D6 and APOE polymorphisms on the efficacy of donepezil in patients with Alzheimer’s disease: a systematic review and meta-analysis. CNS Drugs. 2016;30:899–907.
    1. Ye X., Kong W., Zafar M.I., Chen L.-L. Serum triglycerides as a risk factor for cardiovascular diseases in type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies. Cardiovasc. Diabetol. 2019;18:48.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe