title: Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the variability in stable warfarin maintenance dose in Han Chinese.
abstract: OBJECTIVE
  The aim of this study was to investigate whether any of the single-nucleotide polymorphisms (SNPs) in the POR gene were significantly associated with CYP activity and expression, and could contribute to the total variability in stable warfarin maintenance doses in Han Chinese.
  
  
  METHODS
  A total of 408 patients treated at the First Affiliated Hospital of Sun Yat-Sen University were eligible for the study and had attained a stable warfarin maintenance dose at the start of the investigation. Demographics, warfarin maintenance doses, and concomitant medications were documented. Genomic DNA was extracted from peripheral blood samples and genotyped for ten SNPs (CYP 2C9*2 and *3, CYP4F2 rs2108622, VKORC1 -1639C>T, and potential POR genes of rs10239977, rs3815455, rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY genotyping system.
  
  
  RESULTS
  A predictive model of warfarin maintenance dose was established and indicated that age, gender, body surface area, aspirin use, CYP2C9*3, CYP4F2 rs2108622, VKORC1 -1639C>T, and POR*37 831-35C>T accounted for 42.4 % of dose variance in patients undergoing anticoagulant treatment. The contribution of POR*37 831-35C>T to warfarin dose variation was only 3.9 %.
  
  
  CONCLUSIONS
  For the first time, the SNP POR*37 831-35C>T was confirmed as a minor but statistically significant factor associated with interindividual variation in warfarin maintenance dose in Han Chinese. The POR*37 gene polymorphism should be considered in future algorithms for faster and more reliable achievement of stable warfarin maintenance doses.
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Wu-Tao
authors.initials: WT
authors.lastname: Zeng
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China. lizhx5@mail2.sysu.edu.cn.
authors.forename: Cheng-Hsun
authors.identifier: http://orcid.org/0000-0001-6988-5992
authors.initials: CH
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgangdong Rd, Guangzhou, Guangdong, 510260, People's Republic of China.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Xiu-Ting
authors.initials: XT
authors.lastname: Sun
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan Rd.2, Guangzhou, Guangdong, 510080, People's Republic of China.
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System
keywords: Gene polymorphism; POR; Predictive formula of maintenance dose; Warfarin