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An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban

(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB(1) gene variations may be useful in indivi...

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Autores principales: Roşian, Adela-Nicoleta, Iancu, Mihaela, Trifa, Adrian Pavel, Roşian, Ştefan Horia, Mada, Cristina, Gocan, Cornelia Paula, Niţă, Teodora, Istratoaie, Sabina, Boarescu, Paul-Mihai, Buzoianu, Anca Dana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565454/
https://www.ncbi.nlm.nih.gov/pubmed/32961964
http://dx.doi.org/10.3390/jpm10030133
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author Roşian, Adela-Nicoleta
Iancu, Mihaela
Trifa, Adrian Pavel
Roşian, Ştefan Horia
Mada, Cristina
Gocan, Cornelia Paula
Niţă, Teodora
Istratoaie, Sabina
Boarescu, Paul-Mihai
Buzoianu, Anca Dana
author_facet Roşian, Adela-Nicoleta
Iancu, Mihaela
Trifa, Adrian Pavel
Roşian, Ştefan Horia
Mada, Cristina
Gocan, Cornelia Paula
Niţă, Teodora
Istratoaie, Sabina
Boarescu, Paul-Mihai
Buzoianu, Anca Dana
author_sort Roşian, Adela-Nicoleta
collection PubMed
description (1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB(1) gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB(1) rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB(1) SNPs and the risk of bleeding (p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p > 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB(1) variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.
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spelling pubmed-75654542020-10-26 An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban Roşian, Adela-Nicoleta Iancu, Mihaela Trifa, Adrian Pavel Roşian, Ştefan Horia Mada, Cristina Gocan, Cornelia Paula Niţă, Teodora Istratoaie, Sabina Boarescu, Paul-Mihai Buzoianu, Anca Dana J Pers Med Article (1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB(1) gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB(1) rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB(1) SNPs and the risk of bleeding (p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p > 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB(1) variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban. MDPI 2020-09-18 /pmc/articles/PMC7565454/ /pubmed/32961964 http://dx.doi.org/10.3390/jpm10030133 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roşian, Adela-Nicoleta
Iancu, Mihaela
Trifa, Adrian Pavel
Roşian, Ştefan Horia
Mada, Cristina
Gocan, Cornelia Paula
Niţă, Teodora
Istratoaie, Sabina
Boarescu, Paul-Mihai
Buzoianu, Anca Dana
An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban
title An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban
title_full An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban
title_fullStr An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban
title_full_unstemmed An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban
title_short An Exploratory Association Analysis of ABCB(1) rs1045642 and ABCB(1) rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban
title_sort exploratory association analysis of abcb(1) rs1045642 and abcb(1) rs4148738 with non-major bleeding risk in atrial fibrillation patients treated with dabigatran or apixaban
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565454/
https://www.ncbi.nlm.nih.gov/pubmed/32961964
http://dx.doi.org/10.3390/jpm10030133
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