中国回族人群CYP4F2和VKORC1的基因多态性  

Genetic Variations of CYP4F2 and VKORC1 in Hui Chinese

作　　者：齐光照 韩超[1] 李朵璐[1] 周玉冰[1] QI Guang-zhao;HAN Chao;LI Duo-lu;ZHOU Yu-bing(Department of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部

出　　处：《中国药学杂志》2020年第1期33-38,共6页Chinese Pharmaceutical Journal

基　　金：郑州大学第一附属医院院内青年基金资助(YNQN2017125)

摘　　要：目的考察中国回族人群华法林治疗反应相关基因CYP4F2和VKORC1的基因多态性。方法从159名健康中国回族志愿者的外周血提取DNA,CYP4F2的13个外显子及VKORC1的3个外显子及其外显子-内含子交接处的碱基序列通过多聚酶链反应进行扩增,相应的扩增产物经Sanger测序法进行测序分析。所得基因变异体通过软件HAPLOVIEW进行单体型和连锁不平衡分析。错义突变对蛋白的影响通过3个在线软件Poly Phen-2,SIFT和MutationTaster-2进行预测。结果CYP4F2共有18个基因变异体被发现,内含子和外显子各9个,其中有3个变异体是首次报道,即第1内含子-14G>C,第4外显子5039C>T(p.Ala118Val)和第12外显子18227A>C(p.Glu452Ala)。VKORC1共有9个单核苷酸多态性被发现,其中3个位于外显子区。CYP4F2 Val433Met和VKORC1-1639 G>A的变异体等位基因频率分别是0.370和0.608,与千人基因组人群相比均有显著性差异(P<0.05)。CYP4F2和VKORC1所发现的基因变异体有显著的连锁不平衡。结论中国回族人群CYP4F2和VKORC1的群体遗传学模式具有不同的特征,在使用华法林等药物时应进行药物剂量的相应调整。OBJECTIVE To investigate the genetic variation of warfarin response associated genes cytochrome P4504 F2(CYP4 F2)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 CYP4 F2 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 Poly Phen-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 CYP4 F2 in this study,three of which were novel,ie,-14 G>C in intron 1,5039 C>T(p.Ala118 Val)in exon 4 and 18227 A>C(p.Glu452 Ala)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 CYP4 F2 and VKORC1.Variant allele frequencies of CYP4 F2 Val433 Met(0.370)and VKORC1-1639 G>A(0.608)in the Hui Chinese were significantly different from those of world populations in the 1000 Genomes Project.CONCLUSION Special population genetic patterns of CYP4 F2 and VKORC1 are found in Hui Chinese and these results would be useful information for the precise medication in Hui Chinese.

关 键 词：回族 CYP4F2 VKORC1 基因多态性 

分 类 号：R969[医药卫生—药理学]