Inter and intra ethnic variation of vitamin K epoxide reductase complex and cytochrome P450 4F2 genetic polymorphisms and their prevalence in South Indian population.

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.

Effect of CYP2C9 AND VKORC1 genetic polymorphisms on warfarin dose requirement in south indian population.

Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genetic polymorphisms were strongly associated with warfarin dose requirement in Caucasians, African Americans and other populations. Our aim was to evaluate the effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement in south Indian population. A total of 150 patients on warfarin with stable INR (2- 3.5) for the past 3 months were recruited. The genotypes of CYP2C9*2 and *3 and VKORC1 -1639G>A were compared with mean daily warfarin dose (MDWD). The variant allele frequency of VKORC1 -1639G>A was found to be 10.4% and CYP2C9*2 and CYP2C9*3 were found to be 4.5% and 6.6%, respectively. Our study showed that the mean daily warfarin dose is higher in patients with wild type genotypes of CYP2C9 and VKORC1 compared to those with variant genotypes. Multivariate regression analysis revealed that age, body mass index (BMI), duration of therapy and genetic polymorphisms of CYP2C9 and VKORC1 together contribute to 36.1% variability in MDWD in south Indian population.