13个哮喘易感基因型在宁波地区儿童哮喘的分布研究及新预测模型的建立  

Study on the distribution of thirteen asthma susceptible genotypes in children with asthma in Ningbo area and the establishment of a new prediction model

作　　者：林佳辉 解敏 王飞[2] 闫露露[2] 薛江阳 卢燕鸣 李海波[2] LIN Jiahui;XIE Min;WANG Fei;YAN Lulu;XUE Jiangyang;LU Yanming;LI Haibo(Department of Pediatrics,Ningbo Hangzhou Bay Hospital,Ningbo,Zhejiang 315336,China;Key Laboratory of Comprehensive Prevention and Treatment of Birth Defects,Ningbo Women and Children's Hospital,Ningbo,Zhejiang 315000 China;Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200001,China)

机构地区：[1]宁波市杭州湾医院儿科,宁波315336 [2]宁波市妇女儿童医院出生缺陷综合防治重点实验室,宁波315000 [3]上海交通大学医学院附属仁济医院,上海200001

出　　处：《中国优生与遗传杂志》2023年第12期2399-2405,共7页Chinese Journal of Birth Health & Heredity

基　　金：宁波市公益性科技计划项目(2022S035);宁波市科技计划项目(202002N3150);宁波市品牌学科(PPXK2018-06);宁波市医疗卫生高端团队(2022020405)。

摘　　要：目的研究基于GWAS分析方法发现的9个哮喘易感基因位点IL1RL1(rs1420101)、TSLP(rs10455025)、HLA-DQA1(rs9272346)、IL33(rs992969)、SMAD3(rs2033784)、ERBB2(rs2952156)、ZPBP2(rs11557467)、GSDMB(rs2290400)、ORMDL3(rs4795405)及4个既往成熟的儿童哮喘易感基因4位点IL13(rs20541)、IL4(rs2243250)、ADRB2(rs1042713)、FCER1B(rs569108)在宁波地区儿童哮喘的分布研究,探索易感基因位点的相关性并建立新的儿童哮喘易感基因预测模型。方法采用荧光探针熔解曲线法对哮喘实验组293例和正常对照组214例(134例健康儿童和80例健康成人)进行13个易感基因位点基因型分型,并比较不同基因型和等位基因频率与宁波地区儿童哮喘的相关性;比较13个基因位点与宁波地区儿童哮喘IgE阳性组(n=81)和IgE阴性组(n=79)的相关性;应用R语言运行REGENT建立新的儿童哮喘易感基因预测模型,并验证准确性。结果IL1RL1(rs1420101)位点存在突变的TC基因型和TT基因型组合频率高于对照组(P<0.05),IL1RL1(rs1420101)位点T等位基因频率高于对照组(P<0.05);IgE阳性组TSLP(rs10455025)位点存在突变的CA和CC基因型频率低于IgE阴性组(P<0.05);13位点哮喘易感基因预测模型应用R语言运行REGENT预测风险值,以风险值0.915作为区分高低危得到预测指标:准确度60.8%,特异度49.1%,χ2为4.852,P为0.028,OR(95%CI)为1.491(1.044~2.129)。结论IL1RL1(rs1420101)位点与宁波地区儿童哮喘易感存在相关性。TSLP(rs10455025)位点与宁波地区IgE阴性的儿童哮喘存在相关性。由13位点建立的哮喘易感基因预测模型具有一定的哮喘预测效能。Objective This study investigates the role of nine asthma susceptibility gene loci,including IL1RL1(rs1420101),TSLP(rs10455025),HLA-DQA1(rs9272346),IL33(rs992969),SMAD3(rs2033784),ERBB2(rs2952156),ZPBP2(rs11557467),GSDMB(rs2290400),ORMDL3(rs4795405),and four well-established childhood asthma susceptibility gene loci:IL13(rs20541),IL4(rs2243250),ADRB2(rs1042713),FCER1B(rs569108).We aim to assess their distribution in children with asthma in the Ningbo area,explore the correlation between these susceptibility loci,and establish a novel predictive model for childhood asthma susceptibility genes.Methods The genotypes of these 13 susceptibility gene loci were analyzed in 293 asthmatic patients and 214 healthy controls(comprising 134 healthy children and 80 healthy adults)using a fluorescent probe-based melting curve method.We compared the correlation between different genotypes and allele frequencies in children with asthma in the Ningbo area.The comparison was conducted between 13 gene loci associated with the Ig E positive group(n=81)and the Ig E negative group(n=79)in childhood asthma within the Ningbo area.A new prediction model for childhood asthma susceptibility genes was established using the REGENT package in the R language,and its accuracy was subsequently verified.Results The frequencies of TC and TT genotypes of IL1RL1(rs1420101)mutation were significantly higher in the asthma group compared to the control group(P<0.05).Moreover,the T allele frequency of IL1RL1(rs1420101)mutation was also higher in the asthma group(P<0.05).For TSLP(rs10455025),the frequencies of CA and CC genotypes were lower in the Ig E positive group compared to the Ig E negative group(P<0.05).We established a 13-locus asthma susceptibility gene prediction model using REGENT in R language.A risk value of 0.915 was utilized to differentiate between high and low-risk individuals,with an accuracy of 60.8%,specificity of 49.1%,χ~2 value of 4.852,and a significant P of 0.028.The odds ratio(OR)with a 95%confidence interval(CI)was 1.491(1.044-2

关 键 词：儿童哮喘 单核苷酸多态性 IL1RL1 TSLP 哮喘易感基因预测模型 

分 类 号：R725.6[医药卫生—儿科]