The impact of &lt;em&gt;ABCB1&lt;/em&gt; (rs1045642 and rs4148738) and &lt;em&gt;CES1&lt;/em&gt; (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty

Сычев, Д. А.; Леванов, А. Н.; Shelekhova, Tatiana; Бочков, П. О.; Denisenko, Natalia P.; Рыжикова, К. А.; Мирзаев, К. Б.; Grishina, Elena A.; Гаврилов, М. А.; Ramenskaya, G. V.; Козлов, А. В.; Bogoslovsky, Tanya

doi:10.2147/pgpm.s169277

Cited by 44 publications

(54 citation statements)

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“…Similarly, some studies found a significant influence of such polymorphism on the pharmacokinetics of antiviral atazanavir and the clinical outcomes of artemether-lumefantrine antimalarial regimen [37], [45] as well as the chemotherapy clinical outcomes in pediatric patients with leukemia [30], [39]. Furthermore, C3435T rs1045642 polymorphism has even been proven to correlate significantly with amlodipine efficacy and safety, patients' blood pressure after kidney transplantation, and the safety of dabigatran as a thrombin inhibitor [40], [42], [43]. Not only associated with pharmacogenomics because of their function as part of cellular defense mechanism, but C3435T polymorphism also has a significant clinical correlation as a predisposition to depressive disorders [28], [34], [38].…”

Section: Resultsmentioning

confidence: 98%

Allele Frequency of Carbamazepine Major Efflux Transporter Encoding Gene ABCB1 C3435T among Javanese-Indonesian Population

Istikharah¹,

Hartienah²,

Vitriyani³

et al. 2020

Open Access Maced J Med Sci

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BACKGROUND: Genetic variations in ABCB1 gene that encodes P-glycoprotein, the main transporter in the efflux of carbamazepine (CBZ) from the brain cells, can lead to pharmacodynamic and pharmacokinetic variability. Polymorphism of C3435T is widely known to cause protein overexpression that contributes to an increased risk of CBZ resistance. AIM: This study determined the allele frequency distribution of ABCB1 C3435T gene in healthy subjects of the Javanese population as a major ethnic group in Indonesia. METHODS: This cross-sectional study involved 100 healthy volunteers who fulfilled the inclusion criteria. The genotype analysis to detect polymorphism in the targets employed the polymerase chain reaction-restriction fragment length polymorphism method with 5’-TGCTGGTCCTGAAGTTGATCTGTGAAC-3’ as the forward primer and 5’-ACATTAGGCAGTGACTCGATGAAGGCA-3’ as the reverse primer. RESULTS: The frequency of subjects with C allele in ABCB1 C3435T gene reached 53%, higher than that with T allele. CONCLUSION: This finding was nearly the same as that in studies of the populations in China, Turkey, and four countries in the South European continent. It is recommended to conduct further research on the correlation between C3435T polymorphism and CBZ dose variability to provide a comprehensive approach to epilepsy management in patients receiving CBZ.

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Section: Resultsmentioning

confidence: 98%

Allele Frequency of Carbamazepine Major Efflux Transporter Encoding Gene ABCB1 C3435T among Javanese-Indonesian Population

Istikharah¹,

Hartienah²,

Vitriyani³

et al. 2020

Open Access Maced J Med Sci

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“…По результатам четырех исследований [10,13,14,16], включавших 1970 пациентов, носительство аллели С rs2246613 статистически значимо ассоциировано со снижением риска развития любых кровотечений на фоне приема дабигатрана (ОР 0,732, 95%ДИ 0,629-0,851; p<0,001). Тест на гетерогенность не выявил статистически значимых различий между результатами исследований (Q=2,183; p=0,535) (рис.…”

Section: результаты и обсуждениеunclassified

“…Sychev и соавт. [14,15] Эти результаты могут свидетельствовать о перспективе использования данного полиморфизма в качестве генетической детерминанты безопасности дабигатрана, например, при коррекции дозы препарата у пациентов с повышенным риском геморрагических осложнений.…”

Section: результаты и обсуждениеunclassified

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

Abdullaev

Мирзаев

Бочков

et al. 2020

Racionalʹnaâ farmakoterapiâ v kardiologii

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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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“…D. Sychev и соавт. не удалось подтвердить влияния полиморфизма CES1 rs2244613 на пиковую концентрацию дабигатрана у пациентов после тотальной артропластики коленного сустава [61]. К. Мирзаев и соавт.…”

Section: другие ферменты окисленияunclassified

“…В клинических исследованиях D. Sychev и соавт. установили, что генотип TT полиморфизма rs1045642 гена ABCB1 был связан с более высокими пиковыми концентрациями дабигатрана и более высоким риском кровотечения, чем наличие генотипа СС (р<0,008) [61], а также указывают на потенциал фармакогенетического тестирования SNP rs1045642 при назначении амлодипина у пациентов с артериальной гипертензией I-II стадии [65]. Moscow / Москва *¹ [65] Moscow / Москва *² [66] Moscow / Москва [67] Moscow / Москва ³ [68] Laks / Лакцы [22] Dargins / Даргинцы [22] Avars / Аварцы [22] Russians / Русские 4 [69] Nanais / Нанайцы [23] Population / Популяция Prevalence / Распространенность (%) Figure 8.…”

Section: Ihd / ибс [24]unclassified

Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

Мирзаев

Fedorinov

Ivashchenko

et al. 2019

Racionalʹnaâ farmakoterapiâ v kardiologii

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Aim. To summarize Russian studies using pharmacogenetic testing as applied to cardiology.Material and methods. The authors conducted an online search for articles in December 2018 using the following databases: PubMed, Google Scholar, eLIBRARY. The search was carried out by keywords: "Russia", "Russian", "cardiology" together with the terms associated with the polymorphic marker, including: «P450», «CYP2C19», «CYP2D6», «CYP2B1», «CYP2B6», «CYP2Е1», «CYP2C8», «CYP2C9», «CYP3A4», «CYP3A5», «CYP1A1», «CYP1A2», «CYP4F2», «CYP4F1», «ABCB1», «SLCO1B1», «VKORC1», «GGCX», «SULT1A1», «CULT1», «CES1», «gene», «genes», «pharmacogenetics», «pharmacogenomics», «ethnic group».Results. Generalization of information allowed to identify obscure genes that need to be investigated in pharmacogenetic studies. This information can be used for the development of dosing algorithms and the priority choice of drugs, considering the results of pharmacogenetic testing and planning future research.Conclusion. The results of the literature review indicate the importance of studying the most clinically valid and clinically useful pharmacogenetic markers (CYP2C19, CYP2C9, VKORC1, SLCO1B1) among various ethnic groups in the Russian Federation. With the accumulation of evidence of clinical validity and clinical utility of other pharmacogenetic markers (CES1, CYP2D6*4, etc.), the problem of interethnic differences in the carriage of clinically significant polymorphisms of these genes identified in previous studies in the Russian Federation increasingly requires attention. The most promising for the introduction into the clinical practice in the Russian Federation in the near future are polymorphic markers of the CYP2C19, CYP2C9, VKORC1 and SLCO1B1 genes.

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The impact of <em>ABCB1</em> (rs1045642 and rs4148738) and <em>CES1</em> (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty

Cited by 44 publications

References 9 publications

Allele Frequency of Carbamazepine Major Efflux Transporter Encoding Gene ABCB1 C3435T among Javanese-Indonesian Population

Allele Frequency of Carbamazepine Major Efflux Transporter Encoding Gene ABCB1 C3435T among Javanese-Indonesian Population

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

Multi-Ethnic Analysis of Cardiac Pharmacogenetic Markers of Cytochrome P450 and Membrane Transporters Genes in the Russian Population

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