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目的 探讨白细胞介素17A(interleukin-17A,IL-17A)基因启动子区-152G/A和IL-17F基因外显子区7488T/C位点单核苷酸多态性(SNPs)对儿童支气管哮喘及血清总IgE(TIgE)水平的影响.方法 采用聚合酶链反应-限制性片段长度多态性分析方法(PCR-RFLP)检测224例哮喘组儿童[男性152例,女性72例,男女比例为2.11:1,平均年龄(6.11±3.27)岁]和150例健康对照组儿童[男93例,女57例,男女比例为1.63:1,平均年龄(5.61±3.55)岁]IL-17A-152G/A位点和IL-17F 7488T/C位点的基因多态性,并选取部分样本进行PCR产物测序,对酶切结果进行验证;采用贝克曼库尔特实验系统IMMAGE800特定蛋白分析仪以散射比浊法自动检测哮喘组和对照组儿童血清TIgE水平.结果 IL-17A-152G/A在哮喘组和对照组均检出AA、AG、GG三种基因型,此位点的基因型频率分布在两组间的差异有统计学意义(P<0.05).IL-17A-152G/A位点的A变异等位基因携带者患病的危险性高于非携带者,差异有统计学意义(P<0.05).IL-17F 7488T/C位点在哮喘组和对照组均检出TT、TC、CC三种基因型,该位点两组基因型和等位基因的频率分布差异有统计学意义(P<0.05);哮喘组和对照组血清TIgE水平比较差异有统计学意义(P<0.05);IL-17A-152G/A位点哮喘组AA、AG、GG三种基因型对应血清TIgE水平比较差异有统计学意义(P<0.05),AA基因型高于AG基因型(P=0.001)和GG基因型(P=0.001);对照组3种基因型间血清TIgE间比较差异无统计学意义.IL-17F 7488T/C位点哮喘组和对照组TT、TC、CC三组基因型间血清TIgE水平比较差异均无统计学意义(P>0.05);结论 IL-17基因两位点多态性与贵阳地区儿童哮喘的发病有相关性.IL-17A-152G/A多态性位点是贵阳地区哮喘的重要候选基因;变异等位基因A与血清TIgE水平升高相关;IL-17F 7488T/C多态性位点是贵阳地区哮喘的重要候选基因;C等位基因可能对哮喘有弱保护作用;该位点多态性不影响血清TIgE水平的变化.

Objective To investigate the influences of interleukin 17A gene promoter -152G/A (IL-17A -152G/A) and interleukin 17F gene exon 7488 T/C (IL-17F 7488T/C) single nucleotide poly-morphisms on children bronchial asthma and serum total IgE ( TIgE) levels. Methods Genotype distribu-tion of IL-17A-152G/A and IL-17F 7488T/C in 224 children with asthma and 150 healthy subjects was de-tected by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) analysis. Some samples were selected for PCR product sequencing and verification. IMMAGE800 specific protein analyzer from the Beckman Coulter test system was used to automatically detect serum TIgE levels in all subjects. Re-sults Three genotypes of AA, AG and GG were detected at IL-17A -152G/A locus in both asthma and control groups. Differences in genotype frequency distribution were statistically significant between the two groups (P<0. 05). Subjects carrying the variant allele A at IL-17A-152G/A locus were more likely to have asthma than those without (P<0. 05). Three genotypes of TT, TC and CC were detected at IL-17F 7488T/C locus in both asthma and control groups, but differences in the frequency distribution of genotype and al-lele were statistically significant between the two groups (P<0. 05). There was a significant difference in se-rum TIgE levels between asthma and control groups (P<0. 05). In asthma group, patients of AA genotype at IL-17A -152G/A locus had higher serum TIgE levels than those of AG genotype (P=0. 001) and GG geno-type (P=0. 001). No significant difference in serum TIgE levels was found among healthy subjects of the three genotypes in control group. No significant difference in serum TIgE levels was observed among the sub-jects of TT, TC and CC genotypes at IL-17F 7488T/C locus in asthma or control group (P>0. 05). Conclu-sion IL-17 gene polymorphism was correlated with the incidence of asthma in children in Guiyang area. IL-17A -152G/A polymorphism was an important candidate gene for asthma in Guiyang area and the variant al-lele A at -152G/A locus was correlated with increased serum TIgE levels. IL-17F 7488T/C polymorphism was also an important candidate gene for asthma in Guiyang. Children carrying the variant allele C at IL-17F 7488T/C locus showed a lower risk for asthma in Guiyang. IL-17F 7488T/C polymorphism had no influence on serum TIgE levels.