北京地区汉族儿童华法林药物基因多态性的分布与比较  

Distribution and comparison of warfarin drug-gene polymorphism in Han children from Beijing area

作　　者：马晓妹 张明明[1] 王宏茂[1] 孟莉 李晓惠[1,2] MA Xiaomei;ZHANG Mingming;WANG Hongmao;MENG Li;LI Xiaohui(Dept.of Cardiovascular Medicine,Children’s Hospital Affiliated to Capital Institute of Pediatrics,Beijing 100020,China;Dept.of Cardiovascular Medicine,Teaching Hospital of Peking University Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院心血管内科,北京100020 [2]北京大学首都儿科研究所教学医院心血管内科,北京100020

出　　处：《中国药房》2024年第14期1759-1764,共6页China Pharmacy

基　　金：北京市属医院科研培育计划项目(No.PX20231305)。

摘　　要：目的 分析北京地区汉族儿童华法林药物基因多态性的分布特点。方法 收集2019年3月至2023年3月在首都儿科研究所附属儿童医院心血管内科住院患儿VKORC1 rs9923231、CYP2C9 rs1799853^(*)2、CYP2C9 rs1057910^(*)3、CYP4F2 rs2108622、APOE rs429358、APOE rs7412、ABCB1 rs1045642、EPHX1 rs1051740、EPHX1 rs2234922共6个基因9个华法林药物基因位点信息,并与国内外文献已报道人群数据进行比较。结果 北京地区汉族儿童APOE rs429358突变基因型频率男性(19.8%)高于女性(13.5%)(P<0.05)。北京地区汉族儿童VKORC1 rs9923231以纯合突变型(83.3%)为主,与日本儿童(82.2%)一致,高于以白种人为主的英国、瑞典、美国、德国儿童(10.4%~18.3%)(P<0.05)。北京地区汉族儿童CYP2C9以^(*)1/^(*)1型(91.9%)为主,与日本儿童(94.6%)一致,高于以白种人为主的英国、瑞典、美国、德国(66.1%~73.4%)(P<0.05)。EPHX1 rs1051740突变基因型频率成人(78.5%)高于儿童(63.5%)(P<0.05)。结论 北京地区汉族儿童VKORC1 rs9923231、ABCB1 rs1045642突变较多;其华法林药物基因多态性在不同性别、与不同国家以及与中国汉族成人的比较中均存在一定的分布差异,用药时需谨慎使用已报道数据。OBJECTIVE To analyze the distribution characteristics of warfarin drug-gene polymorphism in Han children from Beijing area.METHODS Data of nine warfarin drug-gene loci about VKORC1 rs9923231,CYP2C9 rs1799853~*2 and rs1057910~*3,CYP4F2 rs2108622,APOE rs429358 and rs7412,ABCB1 rs1045642,EPHX1 rs1051740 and rs2234922 were collected from dept.of cardiovascular medicine,Children's Hospital Affiliated to Capital Institute of Pediatrics from March 2019 to March 2023,and the population data reported in domestic and foreign literature were compared.RESULTS In Beijing area,the frequency of APOE rs429358 mutant genotype was higher in males(19.8%) than in females(13.5%)(P<0.05).VKORC1rs9923231 was dominated by homozygous mutant genotype(83.3%),which was consistent with children in Japan(82.2%),and higher than that of predominantly Caucasian children in the UK,Sweden,the United States,and Germany(10.4%-18.3%)(P<0.05);CYP2C9 was dominated by ~*1/~*1 type(91.9%),which was consistent with children in Japan(94.6%),and higher than that of predominantly Caucasian children in the UK,Sweden,the United States,and Germany(66.1%-73.4%)(P<0.05).The frequency of EPHX1 rs1051740 mutant genotype was higher in adults(78.5%) than in children(63.5%)(P<0.05).CONCLUSIONS More mutations of VKORC1 rs9923231 and ABCB1 rs1045642 are found in Han children from Beijing area.The distribution of warfarin drug-gene polymorphisms in Han children from Beijing area is different among different genders,as well as compared with other countries,and Chinese Han adults.Therefore,caution should be exercised when using the reported data.

关 键 词：华法林 基因多态性 药物基因组学 儿童 药物遗传学 

分 类 号：R968[医药卫生—药理学] R973.2[医药卫生—药学]