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


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.
Department of Cardiology, Huashan Hospital, Fudan University , Shanghai , China.
Bo
B
Jin
Yong
Y
Hong
Jun
J
Zhu
Yong
Y
Li
Hai-Ming
HM
Shi
D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D044466:Asian People; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004617:Embolism / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D013927:Thrombosis / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use; D044465:White People
D000925:Anticoagulants; D005819:Genetic Markers; D014859:Warfarin; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
Genetic polymorphism; Meta-analysis; VKORC1; Warfarin