贵阳地区哮喘患儿IL-4Rα基因多态性及其与血清总IgE水平的相关性

Correlation of gene polymorphism of interleukin 4 receptor alpha peptide chain and total serum IgE levels in asthmatic children in Guiyang area

目的探讨贵阳地区支气管哮喘患儿白细胞介素4受体α链（IL-4Rα）基因多态性及其与血清总IgE的相关性。方法以2010年8月至2011年2月于贵阳医学院附属医院确诊的160例哮喘患儿为哮喘组[男96例，女64例，年龄（6．9±3．3）岁]、以同期于该院门诊体检中心体检的143名健康儿童为对照组[男75例，女68例，年龄（4．9±3．9）岁]；两组均用限制性片段长度多态性分析法及等位基因特异性．聚合酶链反应法分别检测其IL-4Rα外显子12区Q576R及外显子5区175V位点的多态性；酶联免疫吸附法检测血清总IgE的水平。比较两组基因型和等位基因频率、血清总IgE及不同基因型、不同组问血清总IgE水平。结果IL-4Rα链Q576R位点和175V位点在哮喘组和对照组均存在AA、AG、GG三种基因型，两个位点的基因型频率在哮喘组和对照组间的分布差异均有统计学意义（X2=30．972、16．776，均P〈0．001）。Q576R和175V多态位点变异等位基因携带者患病危险高于非携带者（X2=33．236、13．845，均P〈0．001）。哮喘组血清总IgE水平显著高于对照组[（312±297）比（61±48）U／ml，t=9．959，P〈0．001]，但两组两个位点的三种基因型间血清总IgE水平差异均无统计学意义（均P〉0．05）。哮喘组及对照组Q576R多态位点变异等位基因携带者与非携带者总IgE水平差异均无统计学意义（t=-0．028、1．279，P=0．978、0．203），对照组175V多态位点变异等位基因携带者与非携带者总IgE水平差异也无统计学意义（t=-0．763，P=0．447），但哮喘组175V多态位点变异等位基因携带者总IgE水平显著高于非携带者（t=-2．112，P=0．036）。结论IL-4Rα 576多态位点和75多态位点均是贵阳地区儿童哮喘的重要候选基因，且175V多态位点携带变异等位基因G的哮喘儿童血清总IgE水平高于非携带的哮喘儿童。

Objective To explore the correlation of gene polymorphism of interleukin 4 receptor alpha chain （IL-4Rα） and total serum IgE levels in children of bronchial asthma in Guiyang area. Methods A total of 160 asthmatic children at Affiliated Hospital, Guiyang Medical College from August 2010 to February 2011 were selected as asthma group. There were 96 males and 64 females with an average age of （6. 9 ＋ 3.3 ） years. During the same period, 143 healthy children from outpatient physical examination center of this hospital were chosen as control group. There were 75 males and 68 females with an average age of （4. 9 ＋ 3.9 ） years. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and allele-specific polymerase chain reaction （AS-PCR） were used to determine the polymorphisms of Q576R on exon 12 and I75V on exon 5 of IL-4Rα in both groups. The total serum IgE levels were determined by enzyme-linked immune sorbent assay （ELISA）. Comparisons of two groups were made for genotype and allele frequency, serum total IgE and different genotypes, different groups of total serum IgE levels. Results Three genotypes of AA, AG and GG existed on Q576R and I75V loci between two groups. The genotypic frequencies of two loci had significant differences in two groups （X2 = 30. 972, 16. 776, both P 〈 0. 001 ）. The subjects with variant allele on Q576R and I75V loci had higher risks for asthma than those without variant allele （ X2 = 33. 236, 13. 845, both F 〈 0. 001 ）. The total serum levels of IgE in asthma group were higher than those in control group （ （312 ±297） vs （61 ＋48） U/ml, t =9. 959, P 〈0. 001）. However, these three genotypes of two loci showed no significant inter-group difference （all P 〉 0. 05 ）. In mutation allele carriers and non-carriers of Q576R locus, total IgE levels showed no significant difference （t = - 0. 028, 1. 279 ; P = 0. 978, 0. 203 ）. Differences in total IgE levels between I75V polymorphic variant allele carriers and non-carriers were also not statistically significant in control group （ t = - 0. 763, P =0. 447）. However, in asthma group, total IgE levels of I75V polymorphic variant allele carriers were significantly higher than those of non-carriers （t = - 2. 112, P = 0. 036）. Conclusions The 576 and 75 loci of IL-4Rα are important candidate genes of asthmatic children in Guiyang area. And the serum total IgE levels of variant allele G at 75 locus in IL-4Rα are higher than those without it.