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Impact of Genetic Factors ( CYP2C9 , VKORC1 and CYP4F2 ) on Warfarin Dose Requirement in the Turkish Population
Author(s) -
Özer Mahmut,
Demirci Yeliz,
Hızel Candan,
Sarıkaya Sabit,
Karaltı İskender,
Kaspar Çiğdem,
Alpan Serdar,
Genç Ece
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12024
Subject(s) - vkorc1 , warfarin , cyp2c9 , turkish population , medicine , maintenance dose , population , vitamin k epoxide reductase , genotype , biology , genetics , atrial fibrillation , environmental health , gene , cytochrome p450 , metabolism
Warfarin has a narrow therapeutic index and displays marked person‐to‐person variation in dose requirement. Functional polymorphisms at candidate genes can therefore offer utility as biomarkers to individualize warfarin treatment. The main objective of this study was to determine whether and to what extent variability in warfarin dose requirements was determined by polymorphisms in CYP2C9 , VKORC1 , CYP4F2 (rs2108622) and EPHX1 (rs2292566) in the T urkish population. Patients (n = 107) who had stable doses and international normalized ratio ( INR s) at their last three consecutive visits were registered. Their demographic factors, concurrent medications, warfarin‐related bleedings or thromboembolisms, smoking, alcohol intake and weekly green vegetable consumption were recorded. From a blood sample, DNA was isolated and genotyped by real‐time PCR for polymorphisms of CYP2C9 , VKORC1 , CYP4F2 and EPHX1 . A regression analysis was used to determine the independent effects of genetic and non‐genetic factors on warfarin dose optimization. In our study, in addition to age, genetic variants of CYP2C9 , VKORC1 and CYP4F2 were found to be significant predictor variables for the maintenance dose for warfarin, explaining 39.3% of dose variability. VKORC1 and CYP2C9 genotypes remain predictor variables of the warfarin dose, and we first found that CYP4F2 (rs2108622) contributes to dose variability in the T urkish population as well. These observations may be of benefit to future translation research with a view to global personalized medicine in regions hitherto understudied such as the T urkish population so as to rationalize initial warfarin dose and reduce the burden of frequent INR measurements.