198例哮喘儿童遗传易感性研究

Study of genetic susceptibility in 198 children with asthma

摘要:

目的：分析4种哮喘相关基因位点在198例哮喘患儿中的单核苷酸多态性（single nucleotide polymorphismr，SNP）分布特点，并探讨其与儿童哮喘遗传易感性及某些哮喘临床表型的关系。方法：采用聚合酶链反应产物电泳鉴定法及实时荧光定量核酸扩增技术检测4种哮喘相关基因位点SNP在198名哮喘患儿和110名健康对照者中的分布，并测定哮喘患儿的血清总IgE（TIgE）水平及血嗜酸性粒细胞比例（%EOS），同时对4种哮喘相关基因位点不同基因型间的TIgE及%EOS分别进行比较分析。结果：血管紧张素转换酶（ACE）基因位点纯合子基因型（DD）频率在哮喘组明显高于健康对照组（χ2=30.667，P＜0.01），且D型等位基因频率在哮喘组亦明显高于健康对照组（χ2=7.151，P<0.01）；各基因位点多态性分布与血清TIgE水平及%EOS均无相关性（均P＞0.05）。结论：ACE基因DD基因型与儿童哮喘的遗传易感性有关，可能是儿童哮喘的危险因素。

Abstract:

OBJECTIVE: To analyze the frequency distribution of single nucleotide polymorphisms (SNPs) of four asthma-related gene loci (ACE I/D; ADRB2 Arg16Gly; TNF-α G-308A; MS4A2 Glu237Gly) in 198 asthmatic children, and to investigate its association with genetic susceptibility to childhood asthma and some clinical phenotypes of asthma. METHODS: Polymerase chain reaction product electrophoresis identification and real-time quantitative PCR detecting system were used to determine the frequency distributions of the SNPs of the four asthma-related gene loci in 198 asthmatic children and 110 healthy controls. The serum total IgE (TIgE) levels and blood eosinophil proportion (%EOS) of the asthmatic children were measured. Different genotypes at the four asthma-related gene loci were compared in terms of TIgE and %EOS. RESULTS: The genotype DD of angiotensin-converting enzyme (ACE) had a significantly higher frequency in the asthmatic children than in the healthy controls (χ2= 30.667, P0.05). CONCLUSIONS: Genotype DD of ACE is related to genetic susceptibility to childhood asthma and may be the risk factor for childhood asthma.