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

doi:10.11852/zgetbjzz2018-26-08-07

中国儿童保健杂志 ›› 2018, Vol. 26 ›› Issue (8): 835-838.DOI: 10.11852/zgetbjzz2018-26-08-07

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

收稿日期:2017-11-07 发布日期:2018-08-10 出版日期:2018-08-10
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)

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

摘要/Abstract

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

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

中图分类号:

R179

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.

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.

参考文献

[1] 魏兵,李奇玉,蒋静,等.孟鲁司特治疗及预防2～5岁儿童哮喘的疗效观察[J].中国医药,2011,6(3):280-281.
[2] Overton NL, Simpson A, Bowyer P.et al.Genetic susceptibility to severe asthma with fungal sensitization[J].Int J Immunogenet,2017,44(3):93-106.
[3] Chiba S, Nakamura Y, Mizuno T.et al.Impact of the genetic variants of GLCCI1 on clinical features of asthmatic patients[J].Clin Respir J,2017,9:1-8.
[4] Kim LH, Chang H,Namgoong S.et al,Genetic variants of the gasdermin B gene associated with the development of aspirin-exacerbated respiratory diseases[J].Allergy Asthma Proc, 2017,38(1):4-12.
[5] 中华医学会儿科学分会呼吸学组, 《中华儿科杂志》编辑委员会.儿童支气管哮喘诊断与防治指南(2016年版)[J].中华儿科杂志,2016,54(3):167-181.
[6] Powell C, Kolamunnage-Dona R, Lowe J,et al.Magnesium sulphate in acute severe asthma in children (MAGNETIC):a randomised, placebo-controlled trial[J].Lancet Respir Med, 2013,1(4):301-308.
[7] 中华医学会儿科分会呼吸学组.白三烯受体拮抗剂在儿童常见呼吸系统疾病中的临床应用专家共识[J].中华实用儿科临床杂志,2016,31(13):973-977.
[8] Sanak M, Simon HU, Szczeklik A.Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma.[J].Lancet,1997,350:1599-1600.
[9] Sayers I, Barton S , Rorke S.et al.Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma[J].Thorax,2003,58(5):417-424.
[10] Van Sambeek R, Stevenson DD, Baldasaro M,et al.5′ Flanking region polymorphism of the gene encoding leukotriene C4 synthase does not correlate with the aspirinintolerant asthma phenotype in the United States[J].J Allergy Clin Immunol,2000,106(1):72-76.
[11] Zhang YG,Huang HL,Huang JC, et al.The -444A/C polymorphism in the LTC4S Gene and the risk of asthma:a meta-analysis[J].Arch Med Res,2012,43(6):444-450.
[12] Amrendra K,Shilpy S,Anurag A, et al.Association of the -1072G/A polymorphism in the LTC4S gene with asthma in an Indian population[J].Int Arch Allergy Immunol,2012,159:271-277.
[13] Kang MJ, Kwon JW, Kim J, et al.Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma[J].Hum Genet,2011,56(4):284-289.
[14] 吴永红, 刘春涛, 王可,等.白三烯C4合成酶基因多态性与支气管哮喘患者抗白三烯治疗反应性的关系[J].中华结核和呼吸杂志,2008,31(11):806-810.
[15] Sayers I, Sampson AP, Ye S,et al.Promoter polymorphism influences the effect of dexamethasone on transcriptional activation of the LTC4 synthase gene[J].Eur J Hum Genet.2003,11(8):619-622.
[16] Asano K, Shiomi T, Hasegawa N,et al.Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT1 antagonist, pranlukast, in Japanese patients with moderate asthma[J].Pharmacogenetics.2002,12(7):565-570.
[17] 蔡畅,周美茜,李玉苹,等.支气管哮喘患者白三烯基因多态性与抗白三烯治疗的相关性研究[J].中华结核和呼吸杂志,2011,34(5):362-366.
[18] Klotsman M, York TP, Pillai SG, et al.Pharmacogenetics of the 5-lipoxygenase biosynthetic pathway and variable clinical response to montelukast[J]Pharmacogenet Genomics,2007,17(3):189-196.

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

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

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	李嘉, 张延赤. 维生素D受体基因多态性及维生素D水平与神经发育障碍关系的研究进展[J]. 中国儿童保健杂志, 2023, 31(5): 516-520.
[2]	李玉, 赵嘉虹, 阚璇. 中国儿童哮喘行动计划的临床应用研究[J]. 中国儿童保健杂志, 2023, 31(2): 185-189.
[3]	徐燕, 刘东海, 梁譞, 郭丽, 戴永利, 张蓉芳. 高原地区儿童哮喘影响因素分析[J]. 中国儿童保健杂志, 2022, 30(7): 796-800.
[4]	陈谊辉, 杨爱叶, 陈鹏, 杨引通. 鼻用激素与孟鲁司特钠联合对腺样体肥大患儿睡眠质量及临床疗效的影响[J]. 中国儿童保健杂志, 2022, 30(1): 93-96.
[5]	董明瑛, 陶炳铜. 白三烯C4合成酶基因多态性与呼吸道合胞病毒毛细支气管炎易感性及疗效的相关性[J]. 中国儿童保健杂志, 2021, 29(5): 545-549.
[6]	李敏, 杨国建, 蓬青梅. T淋巴细胞免疫变化的研究[J]. 中国儿童保健杂志, 2021, 29(3): 335-338.
[7]	胡春霞, 孔令军, 缪鑫霞, 吴建刚. 儿童哮喘血清胱抑素C和体液免疫功能指标变化及其与肺炎支原体感染的相关性研究[J]. 中国儿童保健杂志, 2021, 29(12): 1347-1350.
[8]	刘艳琳, 唐素萍, 兰帝仕, 董李, 林洁琪, 陈燊, 陈岚, 叶雯婧. 药物基因检测指导儿童哮喘个体化治疗的临床观察[J]. 中国儿童保健杂志, 2020, 28(8): 912-916.
[9]	魏红, 宋希元, 刘雪, 曹慧玲, 孔灵玲, 王旭. 还原叶酸载体基因A80G多态性与神经管畸形易感性关系的Meta分析[J]. 中国儿童保健杂志, 2020, 28(7): 774-779.
[10]	杨艳萍, 周艳红, 薛磊. 母亲孕前体重指数及孕期增重与儿童哮喘的相关性研究[J]. 中国儿童保健杂志, 2020, 28(10): 1166-1168.
[11]	徐庆荣, 宋丽, 张艳. CTLA-4基因多态性与儿童支气管哮喘易感性及外周血IFN-γ、IL-4和IgE的关系[J]. 中国儿童保健杂志, 2020, 28(1): 32-36.
[12]	付岭岭,黄凤艳,高瀚,王志萍. 大气污染与儿童哮喘研究文献计量学分析[J]. 中国儿童保健杂志, 2019, 27(2): 178-182.
[13]	常绍鸿,栾斌,张卫星. 内皮型一氧化氮合成酶基因多态性与早产儿脑病的相关性研究[J]. 中国儿童保健杂志, 2019, 27(2): 205-207.
[14]	王卉, 黄秋芳, 张立红, 任明. 实行中国儿童哮喘行动计划对保定地区支气管哮喘儿童临床管理效果观察[J]. 中国儿童保健杂志, 2019, 27(12): 1351-1354.
[15]	戚小兵, 於娟娟, 钟洁琼, 周翔, 吴华娟. 珠海地区NRXN1和NLGN1基因多态性与儿童孤独症的关联性研究[J]. 中国儿童保健杂志, 2019, 27(1): 19-22.