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

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 ca...

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Autores principales: Mohammed Alkreathy, Huda, Mohammed Eid Alsayyid, Khlood, Alaama, Jumana Y., Al Ghalayini, Kamal, Karim, Shahid, Esmat, Ahmed, Damanhouri, Zoheir A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499297/
https://www.ncbi.nlm.nih.gov/pubmed/32994732
http://dx.doi.org/10.1016/j.sjbs.2020.06.022
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author Mohammed Alkreathy, Huda
Mohammed Eid Alsayyid, Khlood
Alaama, Jumana Y.
Al Ghalayini, Kamal
Karim, Shahid
Esmat, Ahmed
Damanhouri, Zoheir A.
author_facet Mohammed Alkreathy, Huda
Mohammed Eid Alsayyid, Khlood
Alaama, Jumana Y.
Al Ghalayini, Kamal
Karim, Shahid
Esmat, Ahmed
Damanhouri, Zoheir A.
author_sort Mohammed Alkreathy, Huda
collection PubMed
description 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.
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spelling pubmed-74992972020-09-28 Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study Mohammed Alkreathy, Huda Mohammed Eid Alsayyid, Khlood Alaama, Jumana Y. Al Ghalayini, Kamal Karim, Shahid Esmat, Ahmed Damanhouri, Zoheir A. Saudi J Biol Sci Original Article 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. Elsevier 2020-10 2020-06-20 /pmc/articles/PMC7499297/ /pubmed/32994732 http://dx.doi.org/10.1016/j.sjbs.2020.06.022 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Mohammed Alkreathy, Huda
Mohammed Eid Alsayyid, Khlood
Alaama, Jumana Y.
Al Ghalayini, Kamal
Karim, Shahid
Esmat, Ahmed
Damanhouri, Zoheir A.
Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study
title Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study
title_full Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study
title_fullStr Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study
title_full_unstemmed Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study
title_short Bisoprolol responses (PK/PD) in hypertensive patients: A cytochrome P450 (CYP) 2D6 targeted polymorphism study
title_sort bisoprolol responses (pk/pd) in hypertensive patients: a cytochrome p450 (cyp) 2d6 targeted polymorphism study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499297/
https://www.ncbi.nlm.nih.gov/pubmed/32994732
http://dx.doi.org/10.1016/j.sjbs.2020.06.022
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