解整合素-金属蛋白酶33基因多态性与儿童支气管哮喘易感性及血浆炎症因子水平的关系

Relationship of a disintegrin and metalloproteinase 33 gene polymorphism withpediatric bronchial asthma susceptibility and plasma inflammatory factors levels

目的探讨解整合素-金属蛋白酶33(ADAM33)基因rs678881、rs2853209单核苷酸多态性(SNP)与儿童支气管哮喘的易感性及血浆炎症因子γ-干扰素、白细胞介素4(IL-4)、IgE水平的关系。方法纳入238例支气管哮喘儿童(哮喘组)及160例健康体检儿童(对照组)。采用聚合酶链反应-限制性片段长度多态性法检测所有研究对象血浆ADAM33基因rs678881及rs2853209位点的基因型,采用酶联免疫吸附法检测血浆γ-干扰素、IL-4、IgE水平。比较两组研究对象ADAM33基因rs678881、rs2853209位点SNP,以及不同基因型支气管哮喘患儿血浆γ-干扰素、IL-4、IgE水平及并发症的发生率。结果哮喘组ADAM33 rs678881 GC、CC基因型的比例以及C等位基因分布频率均高于对照组(均P<0.05);与携带ADAM33 rs678881 GG基因型、G等位基因的儿童相比,携带GC/CC基因型、C等位基因的儿童更易发生支气管哮喘(均P<0.05)。两组ADAM33 rs2853209各基因型比例及等位基因频率差异均无统计学意义(均P>0.05)。与携带ADAM33 rs678881 GG基因型支气管哮喘患儿相比,携带ADAM33 rs678881 GC、CC基因型患儿血浆IL-4、IgE水平更高而γ-干扰素水平更低,且消化道反应发生率更高(均P<0.05);ADAM33 rs2853209各基因型支气管哮喘患儿之间血浆γ-干扰素、IL-4、IgE水平以及并发症发生率比较,差异均无统计学意义(均P>0.05)。结论ADAM33 rs678881 GC、CC基因型及C等位基因增加儿童支气管哮喘的易感性及血浆炎症因子的水平,并可能参与了疾病的进展;而ADAM33 rs2853209 SNP可能与儿童支气管哮喘的易感性及血浆炎症因子的水平无关。

Objective To explore the relationship of single nucleotide polymorphism(SNP)at rs678881 and rs2853209 of a disintegrin and metalloproteinase 33(ADAM33)gene with pediatric bronchial asthma susceptibility and plasma inflammatory factors(γ-interferon,interleukin 4[IL-4]and IgE)levels.Methods Totally 238 bronchial asthma children(asthma group)and 160 healthy children receiving physical examination(control group)were enrolled.Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of rs678881 and rs2853209 loci of ADAM33 gene in the plasma of all subjects,and enzyme-linked immunosorbent assay was used to determine plasmaγ-interferon,IL-4 and IgE levels.The SNPs at rs678881 and rs2853209 loci of ADAM33 gene were compared between the two groups,and a comparison was conducted among bronchial asthma children with different genotypes in terms of plasmaγ-interferon,IL-4 and IgE levels and incidence rate of complications.Results The proportion of GC or CC genotype and C allele distribution frequency of ADAM33 rs678881 were higher in the asthma group than in the control group(all P<0.05);by comparison with children carrying ADAM33 rs678881 GG genotype or G allele,children carrying GC/CC genotype or C allele were prone to develop bronchial asthma(all P<0.05).There was no statistically significant difference between the two groups in genotype proportion or allele distribution frequency of ADAM33 rs2853209(all P>0.05).Compared with bronchial asthma children carrying ADAM33 rs678881 GG genotype,children carrying ADAM33 rs678881 GC or CC genotype yielded higher plasma IL-4 and IgE levels,a lowerγ-interferon level,and a higher incidence rate of gastrointestinal reactions(all P<0.05);no statistically significant difference was found among bronchial asthma children with different genotypes of ADAM33 rs2853209 in plasmaγ-interferon,IL-4 or IgE level,or incidence rate of complications(all P>0.05).Conclusion ADAM33 rs678881 GC or CC genotype and C allele increase the susceptibility of bronchial asthma in children,and may participate in disease progression;but the SNP of ADAM33 rs2853209 may not be related to the susceptibility of bronchial asthma or plasma inflammatory factors levels in children.