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

https://doi.org/10.20996/1819-6446-2020-10-09

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Abstract

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.

About the Authors

S. P. Abdullaev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Sherzod P. Abdullaev – Junior Researcher, Department of Molecular Medicine, Research Institute of Molecular and Personalized Medicine

Barrikadnaya ul. 2/1-1, Moscow,123995



K. B. Mirzaev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Karin B. Mirzaev – MD, PhD, Senior Researcher, Head of Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine

Barrikadnaya ul. 2/1-1, Moscow,123995



P. O. Bochkov
Russian Medical Academy of Continuous Professional Education
Russian Federation

Pavel O. Bochkov – PhD (Biology), Senior Researcher, Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine

Barrikadnaya ul. 2/1-1, Moscow,123995



I. N. Sychev
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Igor N. Sychev – MD, PhD, Assistant, Chair of General and Clinical Pharmacology

Miklukho-Maklaya ul. 6, Moscow, 117198



D. A. Sychev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Dmitriy A. Sychev – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Head of Chair of Clinical Pharmacology and Therapeutics, Rector

Barrikadnaya ul. 2/1-1, Moscow,123995



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For citation:


Abdullaev S.P., Mirzaev K.B., Bochkov P.O., Sychev I.N., Sychev D.A. The CES1 Gene rs2244613 Minor Allele Impact on the Safety Profile of Dabigatran Etexilate: Meta-Analysis. Rational Pharmacotherapy in Cardiology. 2020;16(5):699-705. (In Russ.) https://doi.org/10.20996/1819-6446-2020-10-09

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ISSN 1819-6446 (Print)
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