title: Correlation between single nucleotide polymorphisms in CYP4F2 and warfarin dosing in Chinese valve replacement patients.
abstract: BACKGROUND
  Individuals with implanted mechanical valve prostheses require lifelong anticoagulation therapy with warfarin. The narrow therapeutic index of warfarin makes it difficult to dose and maintain proper anticoagulation. A number of single nucleotide polymorphisms (SNPs) affecting vitamin K or warfarin metabolism have been shown to affect warfarin dosing. Our aim was to study the effect of the CYP4F2 rs2108622-1347 (C > T) variant on warfarin dosing in Chinese patients.
  
  
  METHODS
  We studied 352 patients after heart valve replacement surgery. Warfarin dosing for patients was adjusted to achieve 1.8 ≤ INR ≤ 2.5. We determined the presence of SNPs in CYP4F2 in these patients and investigated their association with warfarin dosing.
  
  
  RESULTS
  We found the frequency of the CYP4F2 rs2108622 C allele was 79.5% and T-allele frequency was 20.5%. The warfarin dose requirement for CC individuals was significantly lower than that for CT or TT individuals (P < 0.05). TT-homozygous individuals required a 0.56 mg/day higher dose of warfarin than their CC counterparts.
  
  
  CONCLUSIONS
  This study demonstrates that CYP4F2 rs2108622 significantly affects the warfarin dose requirement to achieve adequate anticoagulant activity in Chinese individuals. Genotyping of this SNP may allow clinicians to determine the initiation dose for patients following valve-replacement surgery in China.
authors.affiliation: Peking Union Medical College, #1, Minde Road, Donghu District, Nanchang City, Jiangxi Province, 330008, China.
authors.forename: Jie-Hui
authors.initials: JH
authors.lastname: Li
authors.forename: Guo-Guo
authors.initials: GG
authors.lastname: Ma
authors.forename: Shu-Qiang
authors.initials: SQ
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Wu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Xu
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D002681:China; D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D000072470:Cytochrome P450 Family 4; D005260:Female; D006350:Heart Valve Prosthesis; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013927:Thrombosis / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human