Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population
Xiaojuan Yan, Feng Yang, Hanyun Zhou, Hongshen Zhang, Jianfei Liu, Kezhong Ma, Yi Li, Jun Zhu, Jianqiang Ding
Department of Respiratory Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland)
Med Sci Monit 2015; 21:3577-3584
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: Adult, 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