Impact of CYP2C9, VKORC1 and CYP4F2 genetic polymorphisms on maintenance warfarin dosage in Han-Chinese patients: A systematic review and meta-analysis.
BACKGROUND
Warfarin is the most commonly used antithrombotic drug. Single nucleotide polymorphisms (SNPs) of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639 influence warfarin maintenance dosage. We aimed to determine the impact of SNPs of these genes on mean daily warfarin dosage (MDWD) in Han-Chinese patients.


METHODS
Strict literature inclusion criteria were established, and literature searching was performed on PubMed, Embase and Cochrane Library for English articles and CNKI, CBM and Wanfang database for Chinese articles before September 2, 2014. Revman 5.3 was used to analyze the relationship between gene SNPs and MDWD in Han-Chinese subjects.


RESULTS
We included 33 studies researching the impact of gene SNPs on MDWD in Han-Chinese subjects. CYP2C9 *3/*3, *1/*3 and *3 carriers needed a 72% (95% confidence interval [CI]: 62.0%-81.0%), 28% (22.0%-33.0%) and 26% (21.0%-32.0%) lower MDWD, respectively, than CYP2C9 *1/*1 carriers. CYP4F2 TT, CT and T carriers required a 18% (7.0%-30.0%), 7% (7.0%-7.0%) and 11% (7.0%-14.0%) higher MDWD, respectively, than CYP4F2 CC carriers. VKORC1 1173 CC, CT and C carriers required a 98% (78.0%-118.0%), 49% (37.0%-62.0%) and 56% (44.0%-67.0%) higher MDWD, respectively, than VKORC1 1173 TT carriers. VKORC1-1639 GG, GA and G carriers needed a 101% (53.0%-149.0%), 40% (36.0%-45.0%) and 38% (35.0%-42.0%) higher MDWD, respectively, than VKORC1-1639 AA carriers.


CONCLUSIONS
This meta-analysis is the first to report the relationship between genotypes and MDWD among Han-Chinese patients. The results showed that SNPs of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639 significantly influenced the MDWD in Han-Chinese patients.
Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350001, PR China.
Jinhua
J
Zhang
Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou 350001, PR China.
Zhijie
Z
Chen
Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou 350001, PR China.
Chunmei
C
Chen
AF, Atrial Fibrillation; AVR, Atrial Valve Replacement; CI, Confidence Interval; CYP2C9; CYP2C9, Cytochrome P450 Complex Subunit 2C9; CYP4F2, Cytochrome P450 Complex Subunit 4F2; DVT, Deep Vein Thrombosis; HVR, Heart Valve Replacement; Han-Chinese; INR, International Normalized Ratio; MD, Mean Difference; MDWD, Mean Daily Warfarin Dose; MHVR, Mechanical Heart Valve Replacement; MVR, Mitral Valve Replacement; Meta-analysis; NVAF, Non Valvular Atrial Fibrillation; PE, Pulmonary Embolism; RHD, Rheumatic Heart Disease; SD, Standard Deviation; SNPs, Single Nucleotide Polymorphisms; VKORC1; VKORC1, Vitamin K Epoxide Reductase Complex Subunit 1; VTE, Venous Thromboembolism; Warfarin