Wu Maolan, Zheng Xiangrong, Huang Juan, Hu Xiaolei
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
Department of Pediatrics, The First Hospital of Changsha, Changsha, China.
Front Cell Dev Biol. 2021 Dec 15;9:759542. doi: 10.3389/fcell.2021.759542. eCollection 2021.
Genome-wide association studies have identified interleukin 33 (), interleukin 1 receptor-like 1 (), interleukin 1 receptor accessory protein () as asthma susceptibility loci in Europeans. IL33, IL1RL1, and IL1RAP constitute a ligand-receptor complex. We analyzed associations of asthma susceptibility, eosinophilic airway inflammation, and response to inhaled corticosteroid (ICS) with single nucleotide polymorphisms (SNPs) of 3 genes encoding IL33, IL1RL1, and its coreceptor IL1RAP in Chinese Han nationality children. A total of 153 non-asthmatic children and 265 asthmatic children who visited the Xiangya Hospital between September 2015 and August 2019 were recruited for this study. Pulmonary function tests, peripheral blood eosinophil counts (PBEC), and fractional exhaled nitric oxide (FeNO) tests were performed before treatment, and 3 months after treatment. Each participant's DNA was extracted from the peripheral blood, and a Mass ARRAY system was used to genotype the SNPs. The T allele of rs4742170 in was associated with a risk of higher FeNO at baseline, and no improvement in FeNO and airway hyperresponsiveness was found after ICS treatment. The A allele of rs10208293 and C allele of rs13424006 in both were associated with lower susceptibility to asthma and lower FeNO. The TT genotype of rs1420101 and AA genotype of rs4142132 in were associated with a greater probability of improvement in PBEC after ICS treatment. IL33-IL1RL1-IL1RAP complex polymorphisms are associated with childhood asthma susceptibility, eosinophilic airway inflammation, and ICS response in Chinese Han children in Hunan. We speculate that IL33-IL1RL1-IL1RAP complex polymorphisms affect the development of asthma, airway inflammation, and subsequent ICS response in childhood.
全基因组关联研究已确定白细胞介素33(IL33)、白细胞介素1受体样1(IL1RL1)、白细胞介素1受体辅助蛋白(IL1RAP)是欧洲人群中的哮喘易感基因座。IL33、IL1RL1和IL1RAP构成一个配体-受体复合物。我们分析了编码IL33、IL1RL1及其共受体IL1RAP的3个基因的单核苷酸多态性(SNP)与中国汉族儿童哮喘易感性、嗜酸性气道炎症及吸入糖皮质激素(ICS)反应之间的关联。本研究共纳入了2015年9月至2019年8月期间到湘雅医院就诊的153名非哮喘儿童和265名哮喘儿童。在治疗前及治疗3个月后进行肺功能测试、外周血嗜酸性粒细胞计数(PBEC)和呼出一氧化氮分数(FeNO)测试。从外周血中提取每位参与者的DNA,并使用Mass ARRAY系统对SNP进行基因分型。IL1RAP基因中rs4742170的T等位基因与基线时较高的FeNO风险相关,且ICS治疗后FeNO和气道高反应性无改善。IL1RL1基因中rs10208293的A等位基因和rs13424006的C等位基因均与较低的哮喘易感性和较低的FeNO相关。IL1RAP基因中rs1420101的TT基因型和rs4142132的AA基因型与ICS治疗后PBEC改善的可能性更大相关。IL33-IL1RL1-IL1RAP复合物多态性与湖南汉族儿童的儿童哮喘易感性、嗜酸性气道炎症及ICS反应相关。我们推测IL33-IL1RL1-IL1RAP复合物多态性影响儿童哮喘的发生发展、气道炎症及随后的ICS反应。