IL-13、IL-4及FCERIB基因多态性对吸入糖皮质激素治疗儿童哮喘疗效的影响

Effects of IL-13,IL-4 and FCERIB gene polymorphisms on the efficacy of asthma in children treated with inhaled corticosteroids

目的 分析IL-13、IL-4及FCERIB基因多态性与吸入糖皮质激素(ICS)治疗儿童哮喘疗效的关系。方法 将2020年1月至2022年1月于绍兴市第二医院就诊的急性发作期哮喘患儿56例作为急性发作期组,慢性持续期哮喘患儿52例作为慢性持续期组,临床缓解期哮喘患儿53例作为临床缓解期组,另选取同期体检健康者60例作为健康人对照组。采用化学发光法检测并分析不同分期患儿治疗前后血清IgE水平。采用实时荧光定量PCR法分析哮喘患儿以及健康人对照组口腔黏膜脱落细胞中IL-13基因rs20541位点、IL-4基因rs2243250位点、FCERIB基因rs569108位点多态性与患儿肺功能[1秒用力呼气容积(FEV1)、1秒用力呼气容积与最大肺活量比值(FEV1/VCmax)、用力呼出50%肺活量时的平均呼气流速(MEF50)]、呼出气一氧化氮(Fe-NO)以及儿童哮喘控制测试量表(C-ACT)评分变化的关系;根据治疗结果将患儿分为控制组49例、部分控制组37例和未控制组19例,比较不同分组间各基因型分布情况。结果 治疗前临床缓解期、慢性持续期、急性发作期哮喘患儿血清IgE水平依次升高(335.42±37.34 IU/mL vs 446.71±40.95 IU/mL vs 681.52±96.57 IU/mL,F=412.128,P<0.05);与治疗前相比,3组患儿治疗后血清IgE水平均降低(335.42±37.34 IU/mL vs 158.71±28.38 IU/mL,446.71±40.95 IU/mL vs 166.92±29.56 IU/mL,681.52±96.57 IU/mL vs 435.17±62.15 IU/mL,t分别为28.195,39.949,15.617,P均<0.05);健康人对照组、临床缓解期、慢性持续期+急性发作期患儿IL-13、IL-4、FCERIB基因表达型差异有统计学意义(χ^(2)分别为9.742,20.340,9.555,P均<0.05);患儿IL-13、IL-4、FCERIB基因各基因型FEV1、VCmax、MEF50、Fe-NO、C-ACT治疗前后差异具有统计学意义(P均<0.05);IL-13基因rs20541位点控制组AA型(4.1%vs 21.1%)、A等位基因比例(9.2%vs 42.1%),IL-4基因rs2243250位点控制组T等位基因比例(17.3%vs 10.5%),FCERIB基因rs569108位点控制组GG型(4.1%vs 31.6%)、G等位基因比例(11.2%vs 36.8%)低于未控制组,差异均有统计学意义(χ^(2)分别为4.902,19.781,7.451,5.127,11.977,P均<0.05)。结论 FCER1B基因rs569108位点、IL-4基因rs2243250位点、IL-13基因rs20541位点多态性与哮喘患儿ICS疗效相关,上述基因位点突变有助于预测哮喘患儿的ICS治疗效果。

Objective To analyze the relationship between interleukin(IL)-13, IL-4 and FCERIB gene polymorphisms and the efficacy of asthma in children treated with inhaled corticosteroids(ICS). Methods Fifty-six children with acute asthma, 52 with chronic persistent asthma, 53 with clinical remission asthma, and 60 healthy volunteers, who visited Shaoxing Second Hospital between January 2020 and January 2022, were enrolled in this study. The levels of their serum IgE were detected by the chemiluminescence method. The gene polymorphisms of IL-13 gene rs20541, IL-4 gene rs2243250, and FCERIB gene rs569108 in the exfoliated cells of their oral mucosa were analyzed by real-time fluorescence quantitative PCR. The correlations of gene polymorphisms with lung functions such as forced expiratory volume in one second(FEV1), the ratio of FEV1 to maximum vital capacity(FEV1/VCmax) and mean expiratory flow rate at 50% of the vital capacity(MEF50), fractional exhaled nitric oxide(Fe-NO) and children′s asthma control test(C-ACT) score were evaluated. According to the treatment results, the children were divided into control group(n=49), partial control group(n=37) and uncontrolled group(n=19), and the distribution of each genotype between the three groups was compared. Results Before treatment, the levels of serum IgE in children with clinical remission asthma, chronic persistent asthma and acute asthma increased successively(335.42±37.34 IU/mL vs 446.71±40.95 IU/mL vs 681.52±96.57 IU/mL, F=412.128, P<0.05). Compared with before treatment, the levels of serum IgE in these children after treatment decreased significantly(335.42±37.34 IU/mL vs 158.71±28.38 IU/mL, t=28.195, P<0.05;446.71±40.95 IU/mL vs 166.92±29.56 IU/mL, t=39.949, P<0.05;681.52±96.57 IU/mL vs 435.17±62.15 IU/mL, t=15.617, P<0.05). There were statistically significant differences in the genotype distribution of IL-13 gene rs20541, IL-4 gene rs2243250 and FCERIB gene rs569108 among healthy volunteers, children with clinical remission asthma, and children with chronic persistent asthma or acute asthma(χ^(2)=9.742, 20.340 and 9.555, respectively, all P<0.05). There were significant differences in FEV1, VCmax, MEF50, Fe-NO and C-ACT of children with different genotypes of IL-13 gene rs20541, IL-4 gene rs2243250 and FCERIB gene rs569108 before and after treatment(all P<0.05). The proportions of genotype AA(4.1% vs 21.1%) and allele A(9.2% vs 42.1%) of IL-13 gene rs20541, allele T(17.3% vs 10.5%) of IL-4 gene rs2243250, and genotype GG(4.1% vs 31.6%) and allele G(11.2% vs 36.8%) of FCERIB gene rs569108 in the control group were significantly lower than those in the uncontrolled group(χ^(2)=4.902, 19.781, 7.451, 5.127 and 11.977, respectively, all P<0.05). Conclusion The gene polymorphisms of IL-13 gene rs20541, IL-4 gene rs2243250, and FCERIB gene rs569108 are associated with the efficacy of ICS in children with asthma, and the mutations of these loci are helpful to predict the efficacy of ICS in children with asthma.