Association of LTC4S gene polymorphisms with childhood asthma and responsiveness to montelukast

doi:10.11852/zgetbjzz2018-26-08-07

journal1 ›› 2018, Vol. 26 ›› Issue (8): 835-838.DOI: 10.11852/zgetbjzz2018-26-08-07

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Association of LTC4S gene polymorphisms with childhood asthma and responsiveness to montelukast

LIAO Shi-e¹,WEI Bing¹,MA Ming¹,WANG Xue-na¹,WEI Ke-lun²,ZHU Hua³,YU Cong¹,ZHAO Song⁴

1 Department of Pediatrics,the General Hospital of Shenyang Military Command,Shenyang,Liaoning 110016,China;
2 Department of Pediatrics,Sheng-Jing Hospital,China Medical University,Shenyang,Liaoning 110004,China;
3 Department of Pediatrics,the First Hospital,China Medical University,Shenyang,Liaoning 110001,China;
4 Medical Laboratory,the General Hospital of Shenyang Military Command,Shenyang,Liaoning 110016,China.

Received:2017-11-07 Online:2018-08-10 Published:2018-08-10
Contact: WEI Bing,E-mail:weib71@sina.com

白三烯C4合成酶基因多态性与儿童哮喘易感性及孟鲁司特疗效关联研究

廖世峨¹, 魏兵¹, 马明¹, 王雪娜¹, 魏克伦², 祝华³, 于聪¹, 赵松⁴

1 沈阳军区总医院儿科,辽宁沈阳 110016;
2 中国医科大学附属盛京医院,辽宁沈阳 110004;
3 中国医科大学附属第一医院儿科,辽宁沈阳 110001;
4 沈阳军区总医院医学实验科,辽宁沈阳 110016

通讯作者: 魏兵,E-mail:weib71@sina.com
作者简介:廖世峨(1991-),男,辽宁人,硕士研究生在读,主要研究方向为儿童哮喘及其精准治疗。
基金资助:
辽宁省科学技术计划项目(2015020444)

Abstract

Abstract: Objective To study the association between the single nucleotide polymorphisms(SNPs) of leukotriene C4 synthase (LTC4S) rs730012 or rs3776944 and the severity, responsiveness to montelukast in childhood asthma, in order to guide clinical prevention and precise treatment. Methods Sequence specific primers-polymerase chain reactions (PCRs) were used to assess the SNPs of 215 asthma children and 228 non-asthma children in the General Hospital of Shenyang Military Command from May 2016 to August 2017.And the associations among the SNPs of rs730012, rs3776944 and pulmonary function,LTE4 in urine,Childhood Asthma Control Test(C-ACT) score were analyzed. Results 1)No significant differences were found in genetype frequency of rs730012 and rs3776944 between case group and control group (χ²=0.079,0.617,both P＞0.05).2) The genetype frequency of A/C and C/C in moderate or severe asthma group was significantly higher than that in control group and mild asthma group(χ²=4.129,6.088,both P＜0.05).3) The improvement of FEF50、FEF75 in A/C and C/C genotype asthma children after treatment were significantly higher than that in asthma childrenwith A/A genotype (all P＜0.05),while the difference was not found in children treated only by budesonide (P＞0.05).4)The efficacy of montelukast was better in asthma children with A/A genotype.Meantime, changes of uriny LTE4 in A/C and C/C genotypes were higher, and significant differences were found in rs730012, rs3776944(all P＜0.05). Conclusion The SNP of LTC4S rs730012 is associated with the severity level of asthma.And the efficacy of montelukast in patients with wild type of rs730012 or rs3776944 is better.

Key words: LTC4S, gene polymorphism, childhood asthma, montelukast, leukotriene receptor antagonists

摘要： 目的研究白三烯C4合成酶(LTC4S)基因 rs730012、rs3776944两个单核苷酸多态性位点(SNPs)与儿童哮喘易感性和孟鲁司特疗效的关系,以指导哮喘早期预防及精准治疗。方法选取2016年5月-2017年8月沈阳军区总医院就诊的哮喘患儿215例为病例组,228例非哮喘儿童为对照组,应用聚合酶链反应(PCR)及测序法对所有研究对象LTC4S rs730012、rs3776944位点进行基因分型,并于孟鲁司特治疗前后进行肺功能、尿LTE4儿童哮喘控制测试问卷(C-ACT)评分。结果 1)病例组与对照组在rs730012及rs3776944 位点基因型频率差异均无统计学意义(χ²=0.079、0.617,P均＞0.05)。2)中重度哮喘组A/C+C/C基因型频率明显高于对照组和轻度哮喘组,差异有统计学意义(χ²=4.129、6.088,P均＜0.05)。3)A/C+C/C基因型哮喘患儿在经过孟鲁斯特钠治疗后FEF50、FEF75改善率明显高于A/A型患儿(P均＜0.05),而单纯应用布地奈德组患儿差异无显著性(P均＞0.05)。4)A/A基因型患儿应用孟鲁司特疗效更佳,较A/C+C/C基因型尿液LTE4改变率高,rs730012和rs3776944位点差异均有统计学意义(P均＜0.05)。结论 LTC4S rs730012 SNP与哮喘严重程度有关,rs730012及rs3776944 SNPs野生型应用孟鲁司特疗效更佳。

关键词: 白三烯C4合成酶, 基因多态性, 儿童哮喘, 孟鲁司特, 白三烯受体拮抗剂

CLC Number:

R179

LIAO Shi-e,WEI Bing,MA Ming,WANG Xue-na,WEI Ke-lun,ZHU Hua,YU Cong,ZHAO Song. Association of LTC4S gene polymorphisms with childhood asthma and responsiveness to montelukast[J]. journal1, 2018, 26(8): 835-838.

廖世峨, 魏兵, 马明, 王雪娜, 魏克伦, 祝华, 于聪, 赵松. 白三烯C4合成酶基因多态性与儿童哮喘易感性及孟鲁司特疗效关联研究[J]. 中国儿童保健杂志, 2018, 26(8): 835-838.

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Association of LTC4S gene polymorphisms with childhood asthma and responsiveness to montelukast

白三烯C4合成酶基因多态性与儿童哮喘易感性及孟鲁司特疗效关联研究

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