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
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References
[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.
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