川崎病合并冠状动脉病变患儿氯吡格雷抵抗与基因变异性的关系  

Relationship between clopidogrel resistance and genetic variability in Kawasaki disease children with coronary artery lesions

作　　者：曹银银 潘其扬 李健 钟晓芳 梁雪村 何岚 储晨 赵趣鸣 赵璐 王凤 孙淑娜 林怡翔 黄国英 刘芳 Cao Yinyin;Pan Qiyang;Li Jian;Zhong Xiaofang;Liang Xuecun;He Lan;Chu Chen;Zhao Quming;Zhao Lu;Wang Feng;Sun Shuna;Lin Yixiang;Huang Guoying;Liu Fang(Cardiovascular Center,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China;Department of Clinical Medicine,Shanghai Medical College,Fudan University,Shanghai 200032,China;Clinical Laboratory Center,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China)

机构地区：[1]国家儿童医学中心,复旦大学附属儿科医院心血管中心,上海201102 [2]复旦大学上海医学院临床医学院,上海200032 [3]国家儿童医学中心,复旦大学附属儿科医院临床检验中心,上海201102

出　　处：《中华儿科杂志》2024年第10期981-988,共8页Chinese Journal of Pediatrics

基　　金：国家自然科学基金(82070513);上海市卫生健康委员会青年课题(20204Y0100)。

摘　　要：目的分析不同年龄段川崎病合并冠状动脉病变(CAL)患儿氯吡格雷代谢相关基因变异性的分布及其对氯吡格雷抗血小板治疗的疗效影响。方法回顾性队列研究。分析2021年1月至2022年8月在复旦大学附属儿科医院心内科住院的46例川崎病合并CAL并接受氯吡格雷治疗患儿的临床资料,包括性别、年龄、体质指数、川崎病病程、CAL严重程度分级和基线血小板计数等。根据发病年龄分为≥2岁和<2岁组;通过血栓弹力图检测患儿血小板抑制率(ADPi)确定血小板的反应性,将患儿分为高治疗血小板反应(HTPR)组和正常治疗血小板反应(NTPR)组,检测患儿CYP2C19、PON1及ABCB1基因变异性分布。采用t检验、单因素方差分析、χ2检验进行组间比较。结果46例川崎病伴CAL患儿中,男34例、女12例,≥2岁37例、<2岁9例,HTPR组25例、NTPR组21例。≥2岁患儿中HTPR 19例、NTPR 18例;<2岁中HTPR 6例、NTPR 3例。基因检测显示46例患儿共92个等位基因,其中CYP2C19*1、CYP2C19*2、CYP2C19*3、CYP2C19*17,PON1192Q、PON1192R,ABCB13435C和ABCB13435T等位基因检出频率分别为59%(54/92)、32%(29/92)、9%(8/92)、1%(1/92)、36%(36/92)、64%(59/92)、63%(58/92)、37%(34/92)。基因型对血小板抑制率的影响结果分析显示,≥2岁中CYP2C19*1/*3患儿的ADPi明显低于CYP2C19*1/*1[(34±15)%比(61±29)%,t=2.18,P=0.036]。PON1192Q纯合、PON1192R杂合和PON1192R纯合患儿的ADPi差异无统计学意义[(40±22)%比(52±33)%比(65±27)%,F=2.17,P=0.130];ABCB13435C纯合、ABCB13435T杂合和ABCB13435T纯合患儿的ADPi差异无统计学意义[(55±34)%比(60±27)%比(49±24)%,F=0.33,P=0.719]。<2岁组中CYP2C19*1/*1、CYP2C19*1/*2与CYP2C19*2/*2患儿的ADPi差异无统计学意义[(40±20)%比(53±37)%比(34±16)%,F=0.37,P>0.05]。CYP2C19*1/*1与CYP2C19*1/*3患儿的ADPi差异无统计学意义[(44±27)%比(42±20)%,t=0.08,P>0.05]。PON1192Q纯合、PON1192R杂合与PON1192R纯合患儿的ADPi差异无统计学意义[45%�ObjectiveTo analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease(KD)children with coronary artery lesions(CAL)across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.MethodsA retrospective cohort study was conducted.Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel,including gender,age,body mass index,course of KD,CAL severity grade,and baseline platelet count.According to their age,the children were divided into≥2-year-old group and<2-year-old group.Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate(ADPi)calculated via thromboelastography,and children were categorized into high on-treatment platelet reactivity(HTPR)and normal on-treatment platelet reactivity(NTPR)groups.Genotypes of CYP2C19,PON1 and ABCB1 were detected.The t test,one-way analysis of variance and Chi-square test were used for intergroup comparison.ResultsAmong the 46 KD children with CAL,34 were male and 12 were female;37 were≥2-year-old and 9 were<2-year-old;25 cases were in the HTPR group and 21 cases were in the NTPR group,with 19 HTPR and 18 NTPR in the≥2-year-old group,and 6 HTPR and 3 NTPR in the<2-year-old group.Genetic analysis showed that 92 alleles among the 46 children,with frequencies of CYP2C19*1,CYP2C19*2,CYP2C19*3,CYP2C19*17,PON1192Q,PON1192R,ABCB13435C,ABCB13435T at 59%(54/92),32%(29/92),9%(8/92),1%(1/92),36%(36/92),64%(59/92),63%(58/92)and 37%(34/92),respectively.Analysis of the impact of genotype on ADPi revealed that in children aged≥2 years,those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype((34±15)%vs.(61±29)%,t=2.18,P=0.036).There were also no significant difference in ADPi among children with PON1192Q homozygous,PON1192R heterozygote and PON11

关 键 词：黏膜皮肤淋巴结综合征 血小板聚集抑制剂 基因型 儿童 

分 类 号：R725.4[医药卫生—儿科]