The impact of VKORC1-1639G > A genetic polymorphism upon warfarin dose requirement in different ethnic populations

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.

Keywords::

• Genetic polymorphism
• Meta-analysis
• VKORC1
• Warfarin

Transparency

Declaration of funding

This study was supported in part by grants from the National Natural Science Foundation in China (81100157).

Declaration of financial/other relationships

B.J., Y.H., J.Z., Y.L., and H.-M.S. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Dr. Ying Shan for her editorial suggestions. The principal investigators had full access to all of the data in the study and take responsibility for the accuracy of the data analysis.