Influence of CYP4F2 genotype on warfarin dose requirement–a systematic review and meta-analysis

• Published in: Thrombosis research Vol. 130; no. 1; pp. 38 - 44
• Main Authors: Liang, Ruijuan, Wang, Chunling, Zhao, Hong, Huang, Jie, Hu, Dayi, Sun, Yihong
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.07.2012; Elsevier
• Subjects: African Continental Ancestry Group - genetics; Alleles; Anticoagulants - administration & dosage; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Blood and lymphatic vessels; Brain; Cardiology. Vascular system; CYP4F2; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450 Family 4; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Dosage Calculations; European Continental Ancestry Group - genetics; Genetics; Genotype; Hematology, Oncology and Palliative Medicine; Hemorrhage - etiology; Hemorrhage - genetics; Humans; Investigative techniques of hemodynamics; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Meta-analysis; Polymorphism, Genetic; Polymorphisms; Risk Factors; Warfarin; Warfarin - administration & dosage; MDWD; Mechanical Heart Valve Replacement; DVT; Prosthetic Valve Replace; Mean Daily Warfarin Dose; Venous Thromboembolic Disease; PVR; Human Liver Microsomes; Aortic Valve Prosthesis; MD; Genetics; MI; Atrial Fibrillation; Mean Difference; VKORC1; Warfarin; AF; CytochromeP450 Complex Subunit2C9; Gamma-glutamyl carboxylase; Arterial Thromboembolic Disease; WMD; International Normalized Ratio; Vitamin K Epoxide Reductase Complex Subunit 1; Myocardial Infarction; MHVR; CytochromeP450 Complex Subunit 14 F2; AVP; NR; Deep Vein Thrombosis; MVP; VTD; HLM; INR; Mitralic Valve Prosthesis; SNP; APOE; EPHX; Single Nucleotide Polymorphism; Poxide Hydrolase; CYP4F2; CI; Polymorphisms; Meta-analysis; CYP2C9; ATD; Weighted Mean Difference; Confidence Interval; GGCX; PE; Not Related; Pulmonary Embolism; ApolipoproteinE; Antivitamin K; Coumarine derivatives; Genotype; Cardiovascular disease; Anticoagulant; Polymorphism
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.11.043

Abstract Introduction Warfarin is a commonly used oral anticoagulant and the dosage is individually adjusted on the basis of the international normalized ratio (INR) monitoring. It is well known that gene polymorphisms of CytochromeP450 (CYP) 2 C9 gene and the vitamin K epoxide reductase complex 1 (VKORC1) were significantly associated with warfarin dose. However, the association between Cytochrome P450 4 F2 (CYP4F2) polymorphism and warfarin dose requirement is still controversial. This study was to investigate the influence of the CYP4F2 polymorphism, V433M (rs2108622) on warfarin dose for patients by meta-analysis. Methods Strict inclusion and exclusion criteria were set, and the studies prior to December 19, 2010 were searched in PubMed, EMBASE and CNKI. References were examined and experts of primary studies were consulted for additional information. Revman 5.0.2 software was used to analyze the relationship between warfarin maintenance dose and CYP4F2 polymorphism Results Thirteen studies were included in the meta-analysis which consisted of Caucasian, Asian and African populations. Compared to individuals with the homozygous CYP4F2 genotype (CC), carriers of CT, TT genotypes required 10.0% (95% confidence interval(CI) 4.0-15.0) and 21.0% (95% CI 9.0-33.0) higher warfarin doses respectively (P value < 0.05). In addition, T carriers required 11.0% (95% CI 6.0-17.0) higher warfarin dose than CC genotype. Conclusions Our study showed that polymorphism of CYP4F2 had a moderate but statistically significant association with the variation of interindividual warfarin dose. However, whether CYP4F2 can improve the prediction of warfarin dose warrants need further investigation when combined with environmental factors.