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19 November 2015 : Clinical Research  

Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

Xiaojuan YanABCD, Feng YangABC, Hanyun ZhouBCD, Hongshen ZhangDEF, Jianfei LiuBEF, Kezhong MaAEF, Yi LiABC, Jun ZhuBCD, Jianqiang DingDEF

DOI: 10.12659/MSM.894414

Med Sci Monit 2015; 21:3577-3584

Abstract

BACKGROUND: VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement.

MATERIAL AND METHODS: A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed.

RESULTS: Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1–1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05).

CONCLUSIONS: VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose.

Keywords: Anticoagulants - administration & dosage, Asian Continental Ancestry Group - genetics, China, Dose-Response Relationship, Drug, Ethnic Groups - genetics, Gene Frequency, Genetic Association Studies, Heart Valve Prosthesis Implantation, Maintenance, Polymorphism, Genetic, Vitamin K Epoxide Reductases - genetics, Warfarin - administration & dosage, young adult

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750