朱双桂 陈强 万慕湲 李岚 朱晓华 李建 熊友健 杜云

【摘要】 目的：探讨儿童哮喘吸入性糖皮质激素疗效及其与GLCCI1、FCER2基因多态性的关系。方法：选取2017年5月-2018年5月在本院呼吸科诊断为支气管哮喘患儿60例为治疗组，并选取同期在本院进行体检的正常健康儿童30名为对照组。治疗组治疗前采用华夏时代的快速基因分析方法检测入选患儿吸入性糖皮质激素（ICS）相关的基因类型（-1106）GLCCI1和（2206）FCER2，检测对照组及治疗组患儿治疗前、治疗24周后血清SIgE水平和血清IL-6、IL-8、IL-10的水平变化，同时对治疗组患儿治疗前后的肺功能FEV1%进行检测。结果：治疗组60例哮喘患儿（-1106）GLCCI1表现基因型有GG基因型（野生纯合子）、GA基因型（杂合子）、AA基因型（突变型纯合子）。治疗组60例哮喘患儿（2206）FCER2基因型有AA基因型（野生纯合子）、AG基因型（杂合子）、GG基因型（突变型纯合子）。治疗组治疗前血清SIgE、IL-6、IL-8水平均高于对照组，IL-10水平低于对照组，差异均有统计学意义（P<0.05）。治疗前，治疗组（-1106）GLCCI1和（2206）FCER2各基因表现型之间的SIgE、IL-6、IL-8、IL-10、FEV1%pred比较，差异均无统计学意义（P>0.05）。治疗后，治疗组（-1106）GLCCI1和（2206）FCER2表现基因型为AA基因型SIgE、IL-6、IL-8水平较治疗前均下降，IL-10、FEV1%pred较治疗前均上升，差异均有统计学意义（P<0.05）。治疗后，治疗组（-1106）GLCCI1表现型为AA基因型且（2206）FCER2表现型也为AA基因型哮喘患儿的血清SIgE、IL-6、IL-8水平较治疗前均明显下降，且明显低于其他类型患儿（P<0.05）。治疗后，治疗组（-1106）GLCCI1表现型为AA基因型且（2206）FCER2表現型也为AA基因型哮喘患儿的IL-10、FEV1%pred均较治疗前升高，且均明显高于其他类型患儿（P<0.05）。结论：儿童哮喘吸入性糖皮质激素疗效与GLCCI1、FCER2基因多态性密切相关，其中（-1106）GLCCI1表现型为AA基因型和（2206）FCER2表现型为AA基因型哮喘儿童吸入性糖皮质激素疗效更佳。

【关键词】 儿童 哮喘 吸入性糖皮质激素 GLCCI1 FCER2 基因多态性

Efficacy Evaluation of Inhaled Glucocorticoids in Children with Asthma and Study on GLCCI1 and FCER2 Gene Polymorphism/ZHU Shuanggui， CHEN Qiang， WAN Muyuan， LI Lan， ZHU Xiaohua， LI Jian， XIONG Youjian， DU Yun. //Medical Innovation of China， 2021， 18（14）： -123

[Abstract] Objective： To investigate the efficacy of inhaled glucocorticoids in children with asthma and its relationship with GLCCI1 and FCER2 gene polymorphisms. Method： A total of 60 children with bronchial asthma diagnosed in the respiratory department of our hospital from May 2017 to May 2018 were selected as the treatment group， 30 healthy children who underwent physical examination in the same period were selected as the control group. In the treatment group， the gene types associated with inhalation glucocorticoids （ICS） （-1106） GLCCI1 and （2206） FCER2 were detected by rapid gene analysis in the Chinese era before treatment. Serum SIgE levels and serum IL-6， IL-8 and IL-10 levels of children in the control group and the treatment group were detected before and after treatment for 24 weeks. Meanwhile， FEV1%pred of lung function in the treatment group before and after treatment was detected. Result： GG genotype （wild homozygous）， GA genotype （heterozygous） and AA genotype （mutant homozygous） were found in 60 asthmatic children （-1106） in the treatment group. The genotypes of FCER2 in the treatment group （2206） were AA genotype （wild homozygous）， AG genotype （heterozygous） and GG genotype （mutant homozygous）. Before treatment， serum SIgE， IL-6 and IL-8 levels in the treatment group were all higher than those in the control group， and IL-10 level was lower than that in the control group， the differences were statistically significant （P<0.05）. Before treatment， there were no statistically significant differences in SIgE， IL-6， IL-8， IL-10

levels and FEV1%pred between （-1106） GLCCI1 and （2206） FCER2 gene phenotypes in the treatment group （P>0.05）. After treatment， the expression genotypes of （-1106） GLCCI1 and （2206） FCER2 in the treatment group were AA genotype SIgE， IL-6 and IL-8 levels decreased compared with before treatment， while IL-10 and FEV1%pred were increased compared with before treatment， the differences were statistically significant （P<0.05）. After treatment， serum levels of SIgE， IL-6 and IL-8 in asthmatic children with AA genotype （-1106）GLCCI1 and AA genotype （2206） FCER2 genotype in the treatment group were significantly lower than those before treatment， and significantly lower than those in other types of children （P<0.05）. After treatment， IL-10 and FEV1%pred in asthmatic children with AA genotype （-1106） GLCCI1 phenotype and AA genotype （2206） FCER2 phenotype were significantly higher than those before treatment， and significantly higher than those of other types （P<0.05）. Conclusion： The efficacy of inhaled glucocorticoids in children with asthma is closely related to GLCCI1 and FCER2 gene polymorphism， and the efficacy of inhaled glucocorticoids in children with asthma with GLCCI1 phenotype and FCER2 phenotype of AA genotype is better.

[Key words] Children Asthma Inhaled glucocorticoids GLCCI1 FCER2 Genetic polymorphism

First-authors address： Jiangxi Childrens Hospital， Nanchang 330006， China

doi：10.3969/j.issn.1674-4985.2021.14.029

吸入性糖皮質激素（ICS）是目前临床最有效的哮喘控制药物[1]。但是临床观察发现，哮喘患儿ICS的疗效具有较明显的个体差异[2]。哮喘患儿ICS后的治疗反应70%与遗传有关[3]。因此，寻找ICS反应性的药物遗传标记指导ICS治疗对改善哮喘疗效具有重要意义。本研究通过比较（-1106）GLCCI1、（2206）FCER2位点基因不同表型哮喘患儿应用ICS治疗后肺功能以及血清SIgE、IL-6、IL-8、IL-10水平的变化，分析（-1106）GLCCI1与（2206）FCER2基因多态性对哮喘患儿ICS治疗后反应的影响，为儿童哮喘的个体化治疗提供可靠的理论依据。现……