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

Pharmacogenomics as a Tool in Addressing Genetic VariationDependent Adverse Drug Reactions

“…The weekly maintenance dose of warfarin needed for embolic atrial fibrillation and deep vein thrombosis patients was discovered to be significantly lower in patients with the ABCB1 3435CT or TT polymorphism type than in those with the ABCB1 3435CC type (Lee and An, 2022). The presence of homozygous or heterozygous T allele which reduces activity of P-gp predisposed the patients to less elimination of warfarin (Lee and An, 2022). In Chinese Han patients with refractory lupus nephritis, a homozygote T allele was associated with increased P-gp expression, while MDR1 CC and CT genotype with lower P-gp expression (Zhou et al, 2021).…”

“…Patients with C allele in C3435T polymorphism of MDR1 gene has been associated with increased risk of drug resistant epilepsy in children (Stasiolek, 2016). The weekly maintenance dose of warfarin needed for embolic atrial fibrillation and deep vein thrombosis patients was discovered to be significantly lower in patients with the ABCB1 3435CT or TT polymorphism type than in those with the ABCB1 3435CC type (Lee and An, 2022). The presence of homozygous or heterozygous T allele which reduces activity of P-gp predisposed the patients to less elimination of warfarin (Lee and An, 2022).…”