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

ABSTRACT: Background:Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. Patients and methods:A total of 60 patients, aged 37-81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). Results:Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. Conclusion:Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.

SUBMITTER: Sychev DA

PROVIDER: S-EPMC6064159 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Project description:PurposeStability in the sagittal plane, particularly regarding anterior cruciate ligament compensation, and postoperative functionality and satisfaction remain issues in total knee arthroplasty. Therefore, this prospective study compared the clinical outcomes between medial-pivot-based and posterior-stabilised total knee arthroplasty based on anterior translation and clinical scores.MethodsTo assess outcomes of total knee arthroplasty for varus osteoarthritis, the anterior translation distance of the tibia relative to the femur was measured at 30 and 60° of flexion using a KS measure Arthrometer at 6 months postoperatively. The 2011 Knee Society Score, Forgotten Joint Score, visual analogue scale for pain, and range of motion were assessed at 6 months and 1 year postoperatively. The correlations among each score, anterior translation distance, range of motion, and visual analogue scale score for pain were investigated.ResultsThe medial-pivot and posterior-stabilised groups comprised 70 and 51 patients, respectively. The medial-pivot group exhibited a significantly shorter anterior translation distance at 60° flexion than the posterior-stabilised group. Furthermore, the medial-pivot group achieved significantly better outcomes regarding the visual analogue scale for pain, 2011 Knee Society Score, and Forgotten Joint Score than the posterior-stabilised group. A significant negative correlation was observed between the anterior translation distance and the function score of the 2011 Knee Society Score, whereas a significant positive correlation was found between the anterior translation distance and flexion angle, and between the extension angle and score of the Forgotten Joint Score or 2011 Knee Society Score. Significant negative correlations were also found between the pain visual analogue scale and both the 2011 Knee Society Score and Forgotten Joint Score.ConclusionIn total knee arthroplasty for osteoarthritis, the medial-pivot group displayed a shorter anterior translation distance than the posterior-stabilised group at 6 months postoperatively. The visual analogue scale score for pain was also significantly lower in the medial-pivot group than that in the posterior-stabilised group at both 6 months and 1 year postoperatively. Because a correlation was observed between the anterior translation distance and the function score, medial-pivot-based total knee arthroplasty was considered to significantly improve postoperative function compared to posterior-stabilised total knee arthroplasty.

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

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