CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population.
BACKGROUND
It is known that warfarin treatment is problematic, due to its narrow therapeutic range and to the great interindividual variability. Numerous papers have shown the important contribution of CYP2C9 and VKORC1 genetic variants to this variability. Recently, a new SNP within the CYP4F2 gene was found associated with warfarin dose in the USA.


OBJECTIVE
The aim of our work was to replicate this study in the Italian population and to assess the new CYP4F2 variant relative contribution in explaining warfarin dose variability with respect to CYP2C9 and VKORC1 genetic variants together with age and weight.


METHODS
CYP4F2 rs2108622 genotyping was performed by allelic discrimination assay by TaqMan technology. Analysis of variance and multiple linear regression analyses were carried out to examine the contribution of genetic and nongenetic factors.


RESULTS
Our TT patients require 5.49 mg/day versus 2.93 mg/day of our CC patients. Analysis of variance indicates that about 7% of mean weekly warfarin dose variance is explained by CYP4F2 genotype. Our linear regression model including CYP4F2, CYP2C9 and VKORC1 genetic variants, age and weight, explains 60.5% of the interindividual variability.


CONCLUSIONS
Our data confirm and strengthen the role of this variant.
Borgiani
Paola
P
Department of Biopathology and Diagnostic Imaging, School of Medicine, Tor Vergata University, Rome, Italy. borgiani@uniroma2.it
Ciccacci
Cinzia
C
Forte
Vittorio
V
Sirianni
Elisabetta
E
Novelli
Lucia
L
Bramanti
Placido
P
Novelli
Giuseppe
G
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy; D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007558:Italy; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D012384:Rome; D020246:Venous Thrombosis / Q000188:drug therapy; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases