Genetic variation and haplotype structure of the gene Vitamin K epoxide reductase complex, subunit 1 in the Tamilian population

Abstract

Objective: To study the genetic variation and haplotype structure of Vitamin K epoxide reductase complex, subunit 1 (VKORC1) gene in the Tamilian population. Materials And Methods: The study was performed on 210 unrelated, healthy volunteers of the Tamilian population, of either sex between the age group of 18-60 years. Five ml of venous blood sample was collected using sodium ethylene diamine tetra acetic acid (EDTA) as anticoagulant. DNA was extracted using phenol-chloroform extraction method. Eight single nucleotide polymorphisms (SNPs) VKORC1 rs9923231 (G), rs7196161 (T), rs2884737 (T), rs17708472 (C), rs9934438 (C), rs8050894 (G), rs23596121 (C), and rs7294 (A) were studied using real-time quantitative Polymerase Chain Reaction (qPCR) method and they were included for constructing five-major haplotype blocks of VKORC1 gene. Results: The major alleles of VKORC1 rs9923231 (G), rs7196161 (T), rs2884737 (T), rs17708472 (C), rs9934438 (C), rs8050894 (G), and rs23596121 (C), were found to be at frequencies of 90.0%, 89.2%, 90.9%, 94.1%, 90.7%, 89.5% and 91.2%, respectively. The variant allele of VKORC1 rs7294 (A) was more frequent (83.6%) in the Tamilian population. The frequencies of haplotypes HAP1 (GTTCCGCA), HAP2 (ACGCTCTG), HAP3 (GTTTCGCG), HAP4 (GTTCCGCG) and HAP5 (GCTCCCCG) were found to be 80.0%, 7.4%, 4.7%, 1.5% and 1.1%, respectively. Conclusion: In the present study the allele- frequency distributions, genotype and haplotype frequencies of the VKORC1 gene was considered. The findings of this study provide the genetic information required for learning the association of VKORC1 genetic variation and oral anticoagulant dose variability among patients receiving oral anticoagulants in the Tamilian population.