Abstract: Objective To investigate the genetic relationship between orosomucoid like 3 (ORMDL3)gene polymorphism and wheezing in preschool children by association analysis based on nuclear family,so as to provide evidence for the prevention of wheezing. Methods A total of 30 preschool wheezing children with positive result of asthma predictive index (API) and 60 biological parents were selected.The poly morphism of genetic loci gene rs7216389 and rs7216558 loci in each group were analyzed by Sanger sequencing.Then rs7216389 and rs7216558 were analyzed by transmission disequilibrium test (TDT) based on family and haplotype relative risk (HRR) for each group with the FBAT 2.0.4 software. Results The rs7216389 and rs7216558 loci of ORMDL3 gene showed exactly the same genotype.TDT analysis showed that under the additive model and stealth model,the genetic marker loci rs7216389 and rs7216558 were associated with preschool wheezing,and allele T was over-transmitted,which was a risk factor for wheezing (Z=2.268,2.250,P<0.05). Under the dominant model,allele C were associated with preschool wheezing (Z=-2.250, P<0.05),which was protection factor for wheezing.HRR analysis showed that under the additive model,the T/T of rs7216389-rs7216558 composition were associated with preschool wheezing (Z=2.000, P<0.05),while the C/C single-fold had a protective effect (Z=-2.000, P<0.05). Conclusion ORMDL3 gene is associated with the occurrence of wheezing in preschool children,and genetic polymorphism of ORMDL3 gene plays an important role in the pathogenesis of wheezing.

Key words: orosomucoid like 3, transmission disequilibrium test, haplotype relative risk, wheezing, association analysis

摘要： 目的 分析类黏蛋白1样蛋白质3(ORMDL3)基因多态性与学龄前儿童喘息之间的遗传关系,为临床治疗提供科学依据。方法 以2016年1月-2017年12月在连云港市妇幼保健院就诊的30例喘息预测指数(API)阳性的学龄前喘息儿童及60例生物学父母作为研究对象,利用Sanger测序技术对各组ORMDL3基因rs7216389、rs7216558位点进行基因多态性分析,应用FBAT 2.0.4软件对rs7216389、rs7216558位点进行基于家系的传递不平衡检验分析(TDT)和单体型相对风险分析(HRR)。结果 ORMDL3基因两个SNP位点rs7216389、rs7216558显示出完全一致的基因型;TDT分析显示,在可加模型和隐形模型下,遗传标记位点rs7216389、rs7216558与学龄前喘息相关联,等位基因T过多传递,为喘息的危险因素(可加模型:Z=2.268,P<0.05,隐形模型:Z=2.250,P<0.05);显性模型下,等位基因C与喘息相关(Z=-2.250,P<0.05),为喘息的保护因素;HRR分析显示,在可加模型下,rs7216389-rs7216558组成的T/T单倍型与喘息相关(Z=2.000,P<0.05),而C/C单倍型则具有保护效应(Z=-2.000, P<0.05)。结论 ORMDL3基因与学龄前儿童喘息的发生相关联,ORMDL3基因遗传多态性在喘息的发病中起重要作用。

关键词: 类黏蛋白1样蛋白质3, 不平衡检验分析, 单体型相对风险分析, 喘息, 关联分析