The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis

Aim. A meta-analysis of studies on the CES1 gene c.1168-33A>C polymorphism (rs2244613) carriage influence on the equilibrium concentration and the risk of bleeding during dabigatran taking.Material and methods. The search was carried out in the Russian Science Citation Index, Google Academy,...

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Main Authors: S. P. Abdullaev, K. B. Mirzaev, P. O. Bochkov, I. N. Sychev, D. A. Sychev
Format: Article
Language:English
Published: Столичная издательская компания 2020-11-01
Series:Рациональная фармакотерапия в кардиологии
Subjects:
Online Access:https://www.rpcardio.online/jour/article/view/2303
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author S. P. Abdullaev
K. B. Mirzaev
P. O. Bochkov
I. N. Sychev
D. A. Sychev
author_facet S. P. Abdullaev
K. B. Mirzaev
P. O. Bochkov
I. N. Sychev
D. A. Sychev
author_sort S. P. Abdullaev
collection DOAJ
description Aim. A meta-analysis of studies on the CES1 gene c.1168-33A>C polymorphism (rs2244613) carriage influence on the equilibrium concentration and the risk of bleeding during dabigatran taking.Material and methods. The search was carried out in the Russian Science Citation Index, Google Academy, Medline PubMed, Embase databases. The meta-analysis included patients who according to the indications (atrial fibrillation, stroke, joint orthopedic surgery) were prescribed dabigatran in various doses. The association was identified in rs2244613 allele C carriers (genotypes AC and CC) and non-carriers (genotype AA). Quantitative synthesis was performed using OpenMetaAnalyst software. In statistical analysis the fixed effects model was used to estimate the influence of the allele C carriage on the any bleeding frequency and the random effects model was used to estimate the influence on the equilibrium plasma concentration level of dabigatran. The homogeneity of the analyzed studies was verified by Cochrane Q-test.Results. The analysis resulted in selection of 5 works matching all meta-analysis inclusion/exclusion criteria. All selected works included 2030 patients in total. The carriage of the rs2246613 allele C was associated with reduction of risk of any bleeding during dabigatran taking (risk ratio [RR] 0.732, 95% confidence interval [CI] 0.629-0.851; p<0.001). The heterogeneity test did not reveal any reliable differences between the study results (Q=2.183; p=0.535). The level of equilibrium residual concentration of dabigatran was not statistically significant lower for the carriers of C allele of the rs2244613 (mean difference -69.324, 95%CI -236.687-98.039; p=0.417). This might be related to the small sample size and the number of studies included in the meta-analysis. The heterogeneity test did not reveal statistically significant differences between studies (Q=0.388; I2=0%, p=0.534).Conclusion. The carriage of minor C allelic variant of rs2244613 reduces the risk of any bleeding during dabigatran taking, however, no significant association with decrease in dabigatran concentration was found.
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spelling doaj.art-1620c53a071141f9bd0579f78f6745712024-04-01T07:43:40ZengСтоличная издательская компанияРациональная фармакотерапия в кардиологии1819-64462225-36532020-11-0116569970510.20996/1819-6446-2020-10-091793The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-AnalysisS. P. Abdullaev0K. B. Mirzaev1P. O. Bochkov2I. N. Sychev3D. A. Sychev4Russian Medical Academy of Continuous Professional EducationRussian Medical Academy of Continuous Professional EducationRussian Medical Academy of Continuous Professional EducationPeoples Friendship University of Russia (RUDN University)Russian Medical Academy of Continuous Professional EducationAim. A meta-analysis of studies on the CES1 gene c.1168-33A>C polymorphism (rs2244613) carriage influence on the equilibrium concentration and the risk of bleeding during dabigatran taking.Material and methods. The search was carried out in the Russian Science Citation Index, Google Academy, Medline PubMed, Embase databases. The meta-analysis included patients who according to the indications (atrial fibrillation, stroke, joint orthopedic surgery) were prescribed dabigatran in various doses. The association was identified in rs2244613 allele C carriers (genotypes AC and CC) and non-carriers (genotype AA). Quantitative synthesis was performed using OpenMetaAnalyst software. In statistical analysis the fixed effects model was used to estimate the influence of the allele C carriage on the any bleeding frequency and the random effects model was used to estimate the influence on the equilibrium plasma concentration level of dabigatran. The homogeneity of the analyzed studies was verified by Cochrane Q-test.Results. The analysis resulted in selection of 5 works matching all meta-analysis inclusion/exclusion criteria. All selected works included 2030 patients in total. The carriage of the rs2246613 allele C was associated with reduction of risk of any bleeding during dabigatran taking (risk ratio [RR] 0.732, 95% confidence interval [CI] 0.629-0.851; p<0.001). The heterogeneity test did not reveal any reliable differences between the study results (Q=2.183; p=0.535). The level of equilibrium residual concentration of dabigatran was not statistically significant lower for the carriers of C allele of the rs2244613 (mean difference -69.324, 95%CI -236.687-98.039; p=0.417). This might be related to the small sample size and the number of studies included in the meta-analysis. The heterogeneity test did not reveal statistically significant differences between studies (Q=0.388; I2=0%, p=0.534).Conclusion. The carriage of minor C allelic variant of rs2244613 reduces the risk of any bleeding during dabigatran taking, however, no significant association with decrease in dabigatran concentration was found.https://www.rpcardio.online/jour/article/view/2303rs2244613dabigatrandabigatran concentrationbleeding riskmeta-analysis
spellingShingle S. P. Abdullaev
K. B. Mirzaev
P. O. Bochkov
I. N. Sychev
D. A. Sychev
The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis
Рациональная фармакотерапия в кардиологии
rs2244613
dabigatran
dabigatran concentration
bleeding risk
meta-analysis
title The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis
title_full The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis
title_fullStr The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis
title_full_unstemmed The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis
title_short The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis
title_sort ces1 gene rs2244613 minor allele impact on the safety profile of dabigatran etexilate meta analysis
topic rs2244613
dabigatran
dabigatran concentration
bleeding risk
meta-analysis
url https://www.rpcardio.online/jour/article/view/2303
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