Work

Impact of ABCB1 C3435T Polymorphism on Treatment Response of Vitamin K Antagonists: A Systematic Review and Meta-analysis

Year: 2022

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: In the United States, approximately 2.7-6.1 million patients had atrial fibrillation (AF) in 2010, and this number is expected to gradually increase to approximately 5.6 to 12 million by 2050.1,2) The vitamin K antagonists (VKAs), warfarin and acenocoumarol, are prescribed for the treatment or prophylaxis of embolic AF or deep vein thrombosis (DVT).Warfarin was commonly prescribed for older individuals, those with a high risk of stroke or bleeding, and patients with many comorbidities.3) These patients are likely to have drugdisorder or drug-drug interactions.It is necessary for patient safety and personal medication therapy to regularly monitor prothrombin time (PT) or the international normalized ratio (INR).VKAs have a narrow therapeutic range and, therefore, levels outside this range increase the risk of thromboem-bolism or bleeding incidences.VKAs are drugs that interact with various medications and foods [4][5][6] and maintenance doses of VKAs are affected by patient age, 7) body weight, 8) clinical conditions, 9,10) and genetic factors.8,11) According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) are known to influence the warfarin dosing algorithm.11) Similarly, the maintenance dose of acenocoumarol is also affected by VKORC1 and CYP2C9 genes.12) In addition to these well-known genes, recent studies have suggested that the ATP-binding cassette subfamily B member 1 (ABCB1) gene affects the maintenance dose of VKAs; however, the ABSTRACTObjective: The aim of this study was to examine the impact of ATP-binding cassette subfamily B member 1 (ABCB1) C3435T polymorphism on the treatment response of patients to vitamin K antagonists (VKAs).Methods: In this systematic review and metaanalysis, the PubMed/Medline, Embase, and Cochrane Library databases were searched for eligible articles for the period up to November 2020.Articles that reported treatment response to VKAs according to the ABCB1 C3435T polymorphism were included in this study.Results: A total of 13 and 9 articles were included in the systematic review and meta-analysis, respectively.The weekly maintenance dose of warfarin was significantly lower in patients with the ABCB1 3435CT or TT polymorphism type than in those with the ABCB1 3435CC type (weighted mean difference [WMD], -2.53 mg/week; 95% confidence interval [CI], -3.64 to -1.43, p<0.001).However, the weekly maintenance dose of acenocoumarol was not significantly associated with the ABCB1 C3435T polymorphism (WMD, 1.02; 95% CI, -0.61 to 2.65, p=0.22).Conclusion: The ABCB1 C3435T polymorphism was significantly associated with the weekly maintenance dose of warfarin.Further research is needed to confirm the association between the ABCB1 C3435T polymorphism and the incidence rate of bleeding events.

Source: Korean Journal of Clinical Pharmacy

DOI: 10.24304/kjcp.2022.32.3.238

Authors: So Yeon Lee, Sook Hee An

Institution: Wonkwang University

Language: English

Topic: Pharmacogenetics and Drug Metabolism

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Wonkwang University