Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population

Sarahí Herrera-González, Denisse Aideé Martínez-Treviño, Marcelino Aguirre-Garza, Magdalena Gómez-Silva, Hugo Alberto Barrera-Saldaña, Rafael Baltazar Reyes León-Cachón

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

© 2017, Spandidos Publications. All rights reserved. Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed. Additionally, association studies were performed to test for a correlation between metabolizing phenotypes and genetic variants. It was observed that carriers of the genotypes A/C and C/T in AGTR1 and BDKRB2 had higher area under the plasma concentration-time curve values from time 0 to the time of the last measurement and from time 0 extrapolated to infinity, and lower values of clearance of the fraction dose absorbed compared with homozygous carriers (P<0.05). Only the C/C genotype of BDKRB2 was associated with the fast metabolizer phenotype. These data suggest that AGTR1 and BDKRB2 are involved in ATV pharmacokinetics; a novel finding that requires confirmation in further studies.
Original languageEnglish
Pages (from-to)579-584
Number of pages6
JournalBiomedical Reports
DOIs
Publication statusPublished - 1 Dec 2017

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Polymorphism
Metabolism
Pharmacokinetics
Genes
Phenotype
Population
Genotype
Bradykinin B2 Receptors
Angiotensinogen
Angiotensin Type 1 Receptor
Pharmacogenetics
Pharmaceutical Preparations
Single Nucleotide Polymorphism
Publications
Assays
Cohort Studies
Nucleotides
Association reactions
Plasmas
Atorvastatin Calcium

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Herrera-González, S., Martínez-Treviño, D. A., Aguirre-Garza, M., Gómez-Silva, M., Barrera-Saldaña, H. A., & León-Cachón, R. B. R. (2017). Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population. Biomedical Reports, 579-584. https://doi.org/10.3892/br.2017.1009
Herrera-González, Sarahí ; Martínez-Treviño, Denisse Aideé ; Aguirre-Garza, Marcelino ; Gómez-Silva, Magdalena ; Barrera-Saldaña, Hugo Alberto ; León-Cachón, Rafael Baltazar Reyes. / Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population. In: Biomedical Reports. 2017 ; pp. 579-584.
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Herrera-González, S, Martínez-Treviño, DA, Aguirre-Garza, M, Gómez-Silva, M, Barrera-Saldaña, HA & León-Cachón, RBR 2017, 'Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population', Biomedical Reports, pp. 579-584. https://doi.org/10.3892/br.2017.1009

Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population. / Herrera-González, Sarahí; Martínez-Treviño, Denisse Aideé; Aguirre-Garza, Marcelino; Gómez-Silva, Magdalena; Barrera-Saldaña, Hugo Alberto; León-Cachón, Rafael Baltazar Reyes.

In: Biomedical Reports, 01.12.2017, p. 579-584.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population

AU - Herrera-González, Sarahí

AU - Martínez-Treviño, Denisse Aideé

AU - Aguirre-Garza, Marcelino

AU - Gómez-Silva, Magdalena

AU - Barrera-Saldaña, Hugo Alberto

AU - León-Cachón, Rafael Baltazar Reyes

PY - 2017/12/1

Y1 - 2017/12/1

N2 - © 2017, Spandidos Publications. All rights reserved. Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed. Additionally, association studies were performed to test for a correlation between metabolizing phenotypes and genetic variants. It was observed that carriers of the genotypes A/C and C/T in AGTR1 and BDKRB2 had higher area under the plasma concentration-time curve values from time 0 to the time of the last measurement and from time 0 extrapolated to infinity, and lower values of clearance of the fraction dose absorbed compared with homozygous carriers (P<0.05). Only the C/C genotype of BDKRB2 was associated with the fast metabolizer phenotype. These data suggest that AGTR1 and BDKRB2 are involved in ATV pharmacokinetics; a novel finding that requires confirmation in further studies.

AB - © 2017, Spandidos Publications. All rights reserved. Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed. Additionally, association studies were performed to test for a correlation between metabolizing phenotypes and genetic variants. It was observed that carriers of the genotypes A/C and C/T in AGTR1 and BDKRB2 had higher area under the plasma concentration-time curve values from time 0 to the time of the last measurement and from time 0 extrapolated to infinity, and lower values of clearance of the fraction dose absorbed compared with homozygous carriers (P<0.05). Only the C/C genotype of BDKRB2 was associated with the fast metabolizer phenotype. These data suggest that AGTR1 and BDKRB2 are involved in ATV pharmacokinetics; a novel finding that requires confirmation in further studies.

U2 - 10.3892/br.2017.1009

DO - 10.3892/br.2017.1009

M3 - Article

SP - 579

EP - 584

JO - Biomedical Reports

JF - Biomedical Reports

SN - 2049-9434

ER -

Herrera-González S, Martínez-Treviño DA, Aguirre-Garza M, Gómez-Silva M, Barrera-Saldaña HA, León-Cachón RBR. Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population. Biomedical Reports. 2017 Dec 1;579-584. https://doi.org/10.3892/br.2017.1009