ABSTRACT
OBJECTIVE: To investigate the genetic variation of warfarin response associated genes cytochrome P450 4F2 (CYP4F2) and vitamin K epoxide reductase complex subunit 1 (VKORC1) in Hui Chinese. METHODS: Genomic DNA was extracted from 159 healthy Hui Chinese volunteers and 13 exons of CYP4F2 and three exons of VKORC1 and the exon-intron junction were amplified by polymerase chain reaction and sequenced subsequently through Sanger′ sequencing method. Functional prediction of the non-synonymous SNPs was performed by PolyPhen-2, SIFT and MutationTaster-2. Linkage disequilibrium (LD) was assessed for each genetic variant using HAPLOVIEW. RESULTS: There were 18 genetic variants (nine in the introns and nine in the exons) identified in CYP4F2 in this study, three of which were novel, ie, -14G>C in intron 1, 5039C>T (p.Ala118Val) in exon 4 and 18227A>C (p.Glu452Ala) in exon 12. Nine single nucleotide polymorphisms (SNPs) were detected in VKORC1, three of which were in the exons. Strong LD was found in the identified variants of CYP4F2 and VKORC1. Variant allele frequencies of CYP4F2 Val433Met (0.370) and VKORC1-1639G>A (0.608) in the Hui Chinese were significantly different from those of world populations in the 1 000 Genomes Project. CONCLUSION: Special population genetic patterns of CYP4F2 and VKORC1 are found in Hui Chinese and these RESULTS: would be useful information for the precise medication in Hui Chinese.