药物代谢酶细胞色素P450单核苷酸多态性影响哮喘儿童吸入皮质醇激素疗效研究  

Effects of single nucleotide polymorphism of drug metabolizing enzyme cytochrome P450 on the efficacy of inhaled cortisol hormone in asthmatic children

作　　者：朱丽 魏兵 廖世峨 张超 郑晓宇 刘亚军 ZHU Li;WEI Bing;LIAO Shi'e;ZHANG Chao;ZHENG Xiaoyu;LIU Yajun(Department of Paediatrics,General Hospital of Northern Theater Command Postgraduate Training Base,Jinzhou Medical University;Department of Paediatrics,General Hospital of Northern Theater Command,Jinzhou Medical University,Shenyang 110016,Liaoning,China)

机构地区：[1]锦州医科大学北部战区总医院研究生培养基地儿科 [2]北部战区总医院儿科,辽宁沈阳110016

出　　处：《中国临床药理学与治疗学》2023年第5期536-543,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：辽宁省科技厅民生科技计划项目(2021JH2/10300060);沈阳市科技计划项目(20-205-4-062)。

摘　　要：目的:探讨哮喘儿童及健康儿童细胞色素P450酶3A5(CYP3A5)基因rs776746和rs15524单核苷酸多态性(SNPs),阐明儿童哮喘易感性及不同基因型哮喘儿童吸入糖皮质激素(ICS)临床疗效间关系。方法:对2016年10月至2020年10月就诊于北部战区总医院东北地区符合纳入标准的79例汉族哮喘患儿(病例组)及100例健康儿童(对照组)行CYP3A5基因rs776746、rs15524位点多态性检测,并对基因型及等位基因分析,连锁分析。对病例组给予吸入用糖皮质激素雾化吸入3个月,于入组时及治疗后测定肺功能及呼出气一氧化氮(FeNO),在治疗后做哮喘控制评分C-ACT/ACT,从而比较不同基因型患病情况及以上检测指标评分差异。结果:rs776746及rs15524位点存在完全连锁不平衡。CYP3A5基因rs776746位点存在T/T、T/C和C/C 3种基因型。不同基因型在病例组与对照组间频存在统计学差异(χ^(2)=9.121,P=0.010),T/C型患哮喘概率是T/T型的6.345倍(P=0.007),C/C型患哮喘概率是T/T型的3.864倍(P=0.04),变异型患哮喘概率是野生型的4.682倍(P=0.011);rs15524位点存在A/A、A/G和G/G 3种基因型。不同基因型在病例组与对照组间频率存在统计学差异(χ^(2)=9.121,P=0.010),A/A型患哮喘概率是G/G型的3.864倍(P=0.044),A/G型患哮喘概率是G/G型的6.345倍(P=0.007),对比病例组与对照组G/G型与A/A+A/G型频率时,发现后者患哮喘概率是前者的4.682倍(P=0.011)。rs776746位点变异型FEF50及FEF75实测值占预计值百分比的改善率明显高于野生型(t=-2.499、-3.256,P=0.024、0.019),rs15524位点变异型FEF50及FEF75实测值占预计值百分比的改善率明显低于野生型(t=3.380、2.325,P=0.015、0.042)。rs776746位点变异型C-ACT/ACT评分明显高于野生型组(t=0.571,P=0.037);rs15524位点野生型与变异型C-ACT/ACT评分差异无统计学意义(t=0.486,P=0.545)。结论:CYP3A5基因rs776746、rs15524位点均是儿童哮喘易感位点,rs776746及rs15524位点野生型或变异型与AIM:To elucidate the relationship be-tween childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids(ICS)in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymor-phisms(SNPs)of cytochrome P450 enzyme 3A5(CYP3A5)gene in asthmatic children and healthy children.METHODS:The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 chil-dren(Case group)with asthma of Han nationality and 100 healthy children(Control group)who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020,and genotype,allele and linkage analysis were performed.The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months,and lung function and exhaled breath nitric oxide(FeNO)were measured at entry and after treatment,and asthma control score C-ACT/ACT was done after treatment,so as to compare the preva-lence of different genotypes and the differences in the above test index scores.RESULTS:There was complete linkage disequilibrium at rs776746 and rs15524 loci.There were three genotypes of T/T,T/C and C/C at rs776746 locus of CYP3A5 gene.There were significant differences in the frequency of dif-ferent genotypes between the case group and the control group(χ^(2)=9.121,P=0.010).The probability of asthma in T/C genotype was 6.345 times higher than that in T/T genotype(P=0.007),that in C/C genotype was 3.864 times higher than that in T/T genotype(P=0.044),and that in variant type was 4.682 times higher than that in wild-type(P=0.011);There were three genotypes of A/A,A/G and G/G at rs15524 lo-cus.There were significant differences in the fre-quency of different genotypes between the case group and the control group(χ^(2)=9.121,P=0.010).The probability of asthma of genotype A/A was 3.864 times higher than that of genotype G/G(P=0.044),and the probability of asthma of genotype A/G was 6.345 times higher than that of genotype G/G(P=0.007).When comparing the frequency o

关 键 词：CYP3A5 儿童哮喘 基因多态性 细胞色素P450酶 吸入皮质醇激素 

分 类 号：R968[医药卫生—药理学]