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北京地区汉族儿童华法林药物基因多态性的分布与比较
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马晓妹 1, 2* ,张明明 ,王宏茂 ,孟 莉 ,李晓惠 (1. 首都儿科研究所附属儿童医院心血管内科,北京
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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)
中图分类号 R968;R973+.2 文献标志码 A 文章编号 1001-0408(2024)14-1759-06
DOI 10.6039/j.issn.1001-0408.2024.14.15
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。
关键词 华法林;基因多态性;药物基因组学;儿童;药物遗传学
Distribution and comparison of warfarin drug-gene polymorphism in Han children from Beijing area
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MA Xiaomei ,ZHANG Mingming ,WANG Hongmao ,MENG Li ,LI Xiaohui (1. Dept. of Cardiovascular
Medicine, Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing 100020, China;2. Dept. of
Cardiovascular Medicine, Teaching Hospital of Peking University Capital Institute of Pediatrics, Beijing
100020, China)
ABSTRACT 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). VKORC1
rs9923231 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.
KEYWORDS warfarin; gene polymorphism; pharmacogenomics; children; pharmacogenetics
[1]
华法林是目前世界范围内使用最广泛的口服抗凝 静脉血栓、先天性心脏病矫治术后等 。然而华法林治
剂,在儿童群体中被广泛应用于川崎病合并冠脉瘤、动 疗窗狭窄、个体间剂量差异大,近年来药物基因组学研
究发现,这种差异与基因多态性密切相关。既往研究报
Δ 基金项目 北京市属医院科研培育计划项目(No.PX20231305) 道,在成人患者中,VKORC1、CYP2C9、CYP4F2、APOE、
*第一作者 医师,博士研究生。研究方向:儿童心血管疾病、儿童
EPHX1、ABCB1基因多态性均是导致华法林剂量个体差
抗凝治疗。E-mail:malala11@163.com
# 通信作者 主任医师,博士生导师,博士。研究方向:儿童心血管 异的重要遗传因素 [2―4] 。然而有关儿童华法林药物遗传
疾病、儿童抗凝治疗。E-mail:lxhmaggie@pumc.edu.cn 学的研究有限,多集中于VKORC1、CYP2C9这两个对华
中国药房 2024年第35卷第14期 China Pharmacy 2024 Vol. 35 No. 14 · 1759 ·