LTC4S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

Research LTC4S Gene Polymorphisms on the Efficacy of Montelukast in the Treatment of Bronchial Asthma in Han Chinese Children

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4~13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,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(P<0.05)。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(P<0.05),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统计学意义(P<0.05);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(P<0.05),但通气肺功能指标较治疗前差异无统计学意义(P>0.05);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。

Objective:To investigate the effect of single nucleotide polymorphism(SNP)at rs730012 of leukotriene C4 synthase(LTC4S)gene on the efficacy of Montelukast in the treatment of bronchial asthma in Han Chinese children.Methods:A total of 100 children with bronchial asthma aged 4 to 13 years were selected 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 treated 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 divided into AA,AC and CC,and the distribution of each genotype was consistent with genetic balance.After 6 weeks and 12 weeks of treatment,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(P<0.05).The differences in each index of ventilatory lung function and pulsed shock lung function at 6 weeks of treatment in children with type AA were statistically significant compared with those before treatment(P<0.05).At 12 weeks of treatment,there were statistically significant differences in the airway ventilation lung function indexes FEV1,PEF,FVC and pulse shock lung function indexes Zat5,Rat5,Rat20,Rat10,Rat15 and resonance frequency compared with those before treatment(P<0.05).Zat5,Rat5,Rat10 at 6 weeks of treatment and Zat5,Rat5,Rat10,Rat15,resonance frequency improvement at 12 weeks of treatment were better than before treatment for AC type(P<0.05),but the difference in ventilation lung function index was not statistically significant compared with before treatment(P>0.05).There were only 3 cases of CC type in this study,and the comparison was not statistically significant.Conclusion:The SNP at the LTC4S(rs730012)locus was correlated with the efficacy of montelukast,with individuals carrying the A allele having better efficacy against montelukast.