title: Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis.
abstract: A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
authors.affiliation: Division of Internal Medicine C, Department of Medicine, University Hospital of Verona, Verona, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Danese
authors.forename: M
authors.initials: M
authors.lastname: Montagnana
authors.forename: J A
authors.initials: JA
authors.lastname: Johnson
authors.forename: A E
authors.initials: AE
authors.lastname: Rettie
authors.forename: C F
authors.initials: CF
authors.lastname: Zambon
authors.forename: S A
authors.initials: SA
authors.lastname: Lubitz
authors.forename: G
authors.initials: G
authors.lastname: Suarez-Kurtz
authors.forename: L H
authors.initials: LH
authors.lastname: Cavallari
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Mushiroda
authors.forename: M K
authors.initials: MK
authors.lastname: Kringen
authors.forename: P
authors.initials: P
authors.lastname: Borgiani
authors.forename: C
authors.initials: C
authors.lastname: Ciccacci
authors.forename: N T
authors.initials: NT
authors.lastname: Au
authors.forename: T
authors.initials: T
authors.lastname: Langaee
authors.forename: V
authors.initials: V
authors.lastname: Siguret
authors.forename: M A
authors.initials: MA
authors.lastname: Loriot
authors.forename: H
authors.initials: H
authors.lastname: Sagreiya
authors.forename: R B
authors.initials: RB
authors.lastname: Altman
authors.forename: M H A
authors.initials: MH
authors.lastname: Shahin
authors.forename: S A
authors.initials: SA
authors.lastname: Scott
authors.forename: S I
authors.initials: SI
authors.lastname: Khalifa
authors.forename: B
authors.initials: B
authors.lastname: Chowbay
authors.forename: I M
authors.initials: IM
authors.lastname: Suriapranata
authors.forename: M
authors.initials: M
authors.lastname: Teichert
authors.forename: B H
authors.initials: BH
authors.lastname: Stricker
authors.forename: M
authors.initials: M
authors.lastname: Taljaard
authors.forename: M R
authors.initials: MR
authors.lastname: Botton
authors.forename: J E
authors.initials: JE
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: J F
authors.initials: JF
authors.lastname: Carlquist
authors.forename: B D
authors.initials: BD
authors.lastname: Horne
authors.forename: M T M
authors.initials: MT
authors.lastname: Lee
authors.forename: V
authors.initials: V
authors.lastname: Pengo
authors.forename: G C
authors.initials: GC
authors.lastname: Guidi
authors.forename: P
authors.initials: P
authors.lastname: Minuz
authors.forename: C
authors.initials: C
authors.lastname: Fava
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D015331:Cohort Studies; D003374:Coumarins / Q000008:administration & dosage* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005006:Ethnicity; D006801:Humans; D019934:International Normalized Ratio; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D017594:Publication Bias; D012737:Sex Factors; D064417:Vitamin K Epoxide Reductases
chemical_list: D003374:Coumarins; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases