AI Article Synopsis

Article Abstract

Objective: Published data on the association between vitamin K epoxide reductase complex 1 (VKORC1)-1639G > A polymorphism and warfarin dose requirement are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed.

Methods And Results: Studies were identified in English-language articles by search of PubMed and Embase database (inception to July 2013). A total of 32 prospective clinical trials involving 5005 patients were identified and included for analysis. Overall, the weighted mean maintenance dosage of warfarin in patients with the -1639AA genotype decreased 2.62 mg/d compared with that in the -1639GG genotype patients (95% CI -3.10 to -2.14; P < 0.00001) when 24 eligible studies were pooled into the meta-analysis. Furthermore, significantly lower warfarin dose requirement was found in patients with GA genotype versus GG genotype (WMD, -1.32; 95% CI -1.67 to -0.96; P < 0.00001). In the subgroup analysis by ethnicity, statistically significant lower maintenance dosage of warfarin in patients with the AA genotype versus GG genotype were found in both Caucasians (WMD, -2.47; 95% CI -2.92 to -2.03; P < 0.00001) and Asians (WMD, -2.84; 95% CI -4.57 to -1.11; P = 0.001).

Conclusions: This meta-analysis indicated that the VKORC1-1639G > A genetic polymorphism is associated with the variation of interindividual warfarin dose requirement in different ethnic populations.

Download full-text PDF

Source
http://dx.doi.org/10.1185/03007995.2014.912982DOI Listing

Publication Analysis

Top Keywords

polymorphism warfarin
8
warfarin dose
8
dose requirement
8
impact vkorc1-1639g > a
4
vkorc1-1639g > a genetic
4
genetic polymorphism
4
requirement ethnic
4
ethnic populations
4
populations objective
4
objective published
4

Similar Publications

Despite the high progress that has been made in the field of cardiology, the left ventricular assist device (LVAD) can still cause complications (thrombosis/bleeding) in heart failure (HF) patients after implantation. Complications develop due to the incorrect dose of antithrombotic therapy, due to the influence of the non-physiological shear stress of the device, and also due to inherited genetic polymorphisms. Therefore, the aim of our study is to identify the influence of the genetic polymorphisms on complication development in HF patients with implanted LVADs with prescribed antiplatelet therapy.

View Article and Find Full Text PDF

Warfarin is the most widely used oral anticoagulant in clinical practice. The cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) genotypes are associated with warfarin dose requirements in China. Accurate genotyping is vital for obtaining reliable genotype-guided warfarin dosing information.

View Article and Find Full Text PDF

Implementation of pharmacogenetic testing in clinical care has been slow and with few exceptions is hindered by the lack of real-world evidence on how to best target testing. In this retrospective register-based study, we analyzed a nationwide cohort of 1,425,000 patients discharged from internal medicine or surgical wards and a cohort of 2,178 university hospital patients for purchases and prescriptions of pharmacogenetically actionable drugs. Pharmacogenetic variants were obtained from whole genome genotype data for a subset (n = 930) of the university hospital patients.

View Article and Find Full Text PDF

Vkorc1 polymorphisms of the Norway rats in China: Implications for rodent management and evolutionary origin of anticoagulant resistance mutations.

Sci Total Environ

December 2024

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:

Article Synopsis
  • The rise in use of second-generation anticoagulant rodenticides (SGARs) has sparked concerns about their safety for non-target animals and environmental effects.
  • Research has identified specific mutations in the Vkorc1 gene that lead to anticoagulant resistance in Norway rats, particularly noting three mutations (A26T, C96Y, A140T) found in rat populations across China.
  • Understanding these mutations and their origins can help in developing more effective rodent control strategies, emphasizing the need to adopt less toxic first-generation anticoagulant rodenticides (FGARs) in susceptible areas.
View Article and Find Full Text PDF

Meta-analysis of genome-wide association studies of stable warfarin dose in patients of African ancestry.

Blood Adv

October 2024

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Article Synopsis
  • Warfarin dosing is affected by individual clinical and genetic factors, with a need to explore genetic variants specific to African populations for better dosing guidance.
  • A genome-wide association study (GWAS) focused on 989 warfarin-treated participants from Uganda, South Africa, and Zimbabwe, as well as African American cohorts, found significant genetic variants associated with warfarin response.
  • The study highlighted the importance of the CYP2C9 and VKORC1 genes and identified a new potential genetic locus (MALL) that may impact warfarin response, warranting further research to understand its biological relevance.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!