ABSTRACT
@#Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the genotypes have been strongly associated with warfarin maintenance doses. Especially, it has been accepted in academia that cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 subunit (VKORC1) could affect the warfarin maintenance doses. There are also many other genotypes that were reported to be related to warfarin doses, but the results have been in controversial so far. The studies found that the dose formula which contained the genetic factors and clinical information could accurately predict the maintenance dose of warfarin, however, its usefulness is suspected due to the inconsistent results of clinical trials. Large-sample and multi-center studies are necessary to verify the specific effects of gene and non-gene factors to warfarin dose; at the same time, testing constructed models or building new models help to improve the explained percentages of individual differences.
ABSTRACT
Objective: To study the effect of cytochrome P-450 4F2 (CYP4F2, rs2108622) gene polymorphisms in patients with warfarin for initial doses in 7 days. Methods: A total of 271 patients treated by warfarin were studied. The CYP4F2 gene polymorphisms were assessed by real-time PCR, the average initial warfarin doses in 7 days and the time of international normalized ratio (INR) ifrst arrived to therapeutic range were recorded. The differences of initial warfarin doses and the time of INR ifrst arrived to therapeutic range among CYP4F2 gene polymorphisms of CC, CT and TT genotypes were analyzed by statistical method. Results: The average initial warfarin doses among CYP4F2 polymorphisms of TT and CT/TT were higher than CC, P Conclusion: CYP4F2 polymorphisms inlfuenced the initial warfarin doses in 7 days in relevant patients.
ABSTRACT
BACKGROUND: Genetic variation in the vitamin K epoxide reductase complex (VKORC1) and cytochrome P450 4F2 (CYP4F2) genes were found to be strongly associated with the oral anticoagulant (OA) dose requirement. The distribution of genetic variation in these two genes was found to show large inter‑ and intra‑ethnic difference. MATERIALS AND METHODS: A total of 470 unrelated, healthy volunteers of South Indians of either sex (age: 18‑60 years) were enrolled for the study. A 5 ml of venous blood was collected and the genomic deoxyribonucleic acid (DNA) was extracted by using phenol‑chloroform extraction method. Real‑time quantitative polymerase chain reaction (RT‑PCR) method was used for genotyping. RESULTS: The variant allele frequencies of VKORC1 rs2359612 (T), rs8050894 (C), rs9934438 (T) and rs9923231 (A) were found to be 11.0%, 11.8%, 11.7% and 12.0%, respectively. The variant allele VKORC1 rs7294 was (80.1%) more frequent and the variant allele CYP4F2 * 3 was found to be 41.8% in South Indians. The allele, genotype and haplotype frequencies of VKORC1 and CYP4F2 gene were distinct from other compared HapMap populations (P < 0.0001). CONCLUSION: The findings of our study provide the basic genetic information for further pharmacogenetic based investigation of OA therapy in the population.