1、(8):1902-1912.3 Vestergaard LK,Oliveira DNP,Poulsen TS,et al.Oncom-ineTM comprehensive assay v3 vs.oncomineTM comprehensive assay plusJ.Cancers(Basel),2021,13(20):5230.4 Sigafoos AN,Paradise BD,Fernandze-zapico ME.Hedge-hog/GLI signaling pathway:transduction,regulation and im-plications for diseaseJ
2、.Cancers(Basel),2021,13(14):3410.5Doheny D,Manore SG,Wong GL,et al.Hedgehog signaling and truncated GLI1 in cancerJ.Cells,2020,9(9):2114.6Huang D,Wang Y,Tang J,et al.Molecular mechanisms of suppressor of fused in regulating the hedgehog signalling pathwayJ.Oncol Lett,2018,15(5):6077-6086.7 Zhang J,F
3、an J,Zeng X,et al.Hedgehog signaling in gastro-intestinal carcinogenesis and the gastrointestinal tumor mi-croenvironmentJ.Acta Pharm Sin B,2021,11(3):609-620.8 Zhang Z,Zou Y,Liang M,et al.Suppressor of fused(Sufu)promotes epithelial mesenchymal transition(EMT)in cervi-cal squamous cell carcinomaJ.O
4、ncotarget,2017,8(69):114226-114238.9 Yang H,Fu H,Wang B,et al.Exosomal miR-423-5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancerJ.Mol Carcinog,2018,57(9):1223-1236.【文章编号】1006-6233(2023)04-0555-06LTC4S 基因多态性对孟鲁司特治疗汉族儿童支气管哮喘疗效影响的观察研究王珊珊1,洪菲萍2,杨一民1,
5、石慧莉1,陈茜1,李溦1,黄永莲1(1.福 建 中 医 药 大 学 附 属 厦 门 中 医 院,福建厦门 3610092.福建省厦门市厦门弘爱妇产医院新生儿科,福建厦门 361000)【摘要】目的:研究白三烯 C4 合成酶(LTC4S)基因 rs730012 位点的单核苷酸多态性(SNP)对孟鲁司特治疗汉族儿童支气管哮喘疗效的影响。方法:选取 2019 年 4 月至 2021 年 12 月于厦门中医院儿科就诊的 413 岁汉族支气管哮喘患儿 100 例,采用一代测序法对所有患儿的 LTC4S 基因 rs730012 位点进行检测,比较该位点上的 SNP 情况;同时入组患儿均应用孟鲁司特进行治疗
6、,分别于治疗前及治疗6 周、12 周时进行肺通气功能和脉冲震荡肺功能检测及临床控制水平评估,分析 SNP 与疗效的相关性。结果:LTC4S(rs730012)基因分为 AA、AC、CC 型,各基因型分布均符合遗传平衡。治疗 6 周、12 周时AA 型、AC 型患儿临床症状良好控制率均优于 CC 型,其差异具有统计学意义(P0.05)。AA 型患儿治疗 6 周时通气肺功能及脉冲震荡肺功能各指标较治疗前差异均有统计学意义(P0.05),治疗 12 周时大气道通气肺功能指标 FEV1、PEF、FVC 及脉冲震荡肺功能 Zat5、Rat5、Rat20、Rat10、Rat15、共振频率指标较治疗前差异有
7、统计学意义(P0.05);AC 型治疗 6 周时 Zat5、Rat5、Rat10 及治疗 12 周时 Zat5、Rat5、Rat10、Rat15、共振频率改善优于治疗前(P0.05);CC 型因本研究样本中仅 3 例,比较无统计学意义。结论:LTC4S(rs730012)位点的 SNP 与孟鲁司特疗效有一定相关性,以携带 A 等位基因个体对孟鲁司特疗效较好。【关键词】LTC4S;单核苷酸多态性;支气管哮喘;儿童;孟鲁司特【文献标识码】A 【doi】10.3969/j.issn.1006-6233.2023.04.06Research LTC4S Gene Polymorphisms on th
8、e Efficacy of Montelukast in the Treatment of Bronchial Asthma in Han Chinese ChildrenWANG Shanshan,et al(Xiamen Hospital of Traditional Chinese Medicine,Fujian Xiamen 361009,China)【Abstract】Objective:To investigate the effect of single nucleotide polymorphism(SNP)at rs730012 of leukotriene C4 synth
9、ase(LTC4S)gene on the efficacy of Montelukast in the treatment of bronchial asthma in 555 第 29 卷 第 4 期2023 年 4 月 河 北 医 学HEBEI MEDICINE Vol.29,No.4Apr.,2023 【基金项目】福建省科技厅引导性项目,(编号:2019D012)【通讯作者】洪菲萍Han Chinese children.Methods:A total of 100 children with bronchial asthma aged 4 to 13 years were selec
10、t-ed from the Department of Pediatrics of Xiamen Hospital of Traditional Chinese Medicine from April 2019 to December 2021.The rs730012 site of LTC4S gene in all children was detected by generation sequencing method,and the SNP in this site was compared.At the same time,all enrolled children were tr
11、eated with Montelukast.Pulmonary ventilation function and pulse shock lung function were detected and clinical control level was evaluated before treatment and at 6th week and 12th week of treatment,respectively,to analyze the correlation between SNP and efficacy.Results:LTC4S(rs730012)gene was divi
12、ded into AA,AC and CC,and the distribution of each genotype was consistent with genetic balance.After 6 weeks and 12 weeks of treat-ment,the good control rate of clinical symptoms in children with AA and AC were better than those with CC,and the difference was statistically significant(P0.05).The di
13、fferences in each index of ventilatory lung function and pulsed shock lung function at 6 weeks of treatment in children with type AA were statistically sig-nificant compared with those before treatment(P0.05).At 12 weeks of treatment,there were statistically significant differences in the airway ven
14、tilation lung function indexes FEV1,PEF,FVC and pulse shock lung function indexes Zat5,Rat5,Rat20,Rat10,Rat15 and resonance frequency compared with those before treat-ment(P0.05).Zat5,Rat5,Rat10 at 6 weeks of treatment and Zat5,Rat5,Rat10,Rat15,resonance fre-quency improvement at 12 weeks of treatme
15、nt were better than before treatment for AC type(P0.05).There were only 3 cases of CC type in this study,and the comparison was not statistically signifi-cant.Conclusion:The SNP at the LTC4S(rs730012)locus was correlated with the efficacy of montelukast,with individuals carrying the A allele having
16、better efficacy against montelukast.【Key words】LTC4S;Single nucleotide polymorphism;Bronchial asthma;Children;Monte-lukast 支气管哮喘(以下简称“哮喘”)是儿童最常见慢性呼吸道疾病之一。白三烯受体拮抗剂(leckotriene receptor antagonist,LTRA)是目前除糖皮质激素外,唯一可单独应用的哮喘长期控制药物,其中孟鲁司特是目前最常用的 LTRA 制剂。但目前临床上 LTRA 治疗哮喘患儿存在明显的个体差异,有研究认为,造成此疗效的差异可能与基因多态性有关1。本研究通过对汉族哮喘患儿与孟鲁司特疗效相关的 LTC4S 基因rs730012 位点的 SNP 进行分析,试图从分子水平研究该位点的 SNP 与症状控制情况及肺功能改善情况的相关性,以期为汉族哮喘患儿精准的个体化治疗提供参考和依据。1 资料与方法1.1 研究对象:选取 2019 年 4 月至 2021 年 12 月于厦门中医院儿科就诊的 413 岁汉族支气管哮喘患儿100 例。纳入标准:符
