title: Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population.
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.
authors.affiliation: Department of Respiratory Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland).
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Cardiovascular Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland).
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland).
authors.forename: Hanyun
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Cardiovascular Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland).
authors.forename: Hongshen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland).
authors.forename: Jianfei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei, China (mainland).
authors.forename: Kezhong
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Ministry of Health Beijing Hospital, Beijing, China (mainland).
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medical Department, Henan Provincial Corps Hospital of Chinese People's Armed Police Force, Zhengzhou, Henan, China (mainland).
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Medical Department, Henan Provincial Corps Hospital of Chinese People's Armed Police Force, Zhengzhou, Henan, China (mainland).
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D044466:Asian People / Q000235:genetics; D002681:China; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D008283:Maintenance; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases