VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children

摘要: BACKGROUND Despite substantial evidence supporting a pharmacogenetic approach to warfarin therapy in adults, on the importance of genetics children is limited, particularly for clinical outcomes. We assessed contribution CYP2C9/VKORC1/CYP4F2 genotypes and variation other genes involved vitamin K coagulation pathways dose related outcomes children. PROCEDURE Clinical genetic data 93 (age ≤ 18 years) who received were obtained. DNA was genotyped selected single nucleotide polymorphisms using custom assay. RESULTS With median age 4.8 years, our cohort included more young than most previous studies. Overall, 76.3% variability explained by weight, indication, VKORC1-1639G/A CYP2C9 *2/*3, with accounting 21.1% variability. There strong correlation (R(2) = 0.68; P 4; 0.024) during initiation therapy. CYP2C9*3 carriers also at increased risk major bleeding while receiving (adjusted OR 11.28). An additional variant (rs7089580) significantly associated (P 0.020) multivariate model. CONCLUSIONS This study confirms VKORC1/CYP2C9 dosing pediatric demonstrates an impact factors children. Furthermore, we identified potential relevance