摘要目的 探讨白细胞介素(IL)-4基因启动子区+33C/T位点和IL-13内含子+1923C/T位点单核苷酸多态性与支气管哮喘(简称哮喘)患者易感性的相关性及其对血清总IgE水平的影响.方法 2003年12月至2007年6月应用聚合酶链反应和限制性片段长度多态性(PCR/RFLP)方法对山东的150例汉族哮喘患者(哮喘组)与160名健康人(健康对照组)IL-4基因+33C/T位点和IL-13基因+1923C/T位点的单核苷酸多态性进行检测,应用酶联免疫吸附法(ELISA)测定两组血清总IgE含量.两组各等位基因及基因型频率的比较用X2检验,不同基因型间IgE水平的比较采用两样本t检验.结果 IL-4基因+33C/T位点基因型CC、CT和TT在健康对照组中分布频率分别为43%(68/160)、35%(56/160)和22%(36/160),在哮喘组分布频率分别为18%(27/150)、36%(54/150)和46%(69/150);IL-13基因+1923C/T位点基因型CC、CT和TT在健康对照组中分布频率分别为41%(66/160)、43%(68/160)和16%(26/160),在哮喘组分布频率分别为21%(31/150)、38%(57/150)和41%(61/150).IL-4基因+33C/T位点和IL-13基因+1923C/T位点的各基因型在两组间的分布差异有统计学意义(X2值分别为27.821和26.544,均P<0.01).CT、TT基因型患哮喘的危险性高于CC基因型(X2值分别为21.870和14.206,均P<0.01).IL-4基因+33C/T位点基因型CC、CT和TT在健康对照组中血清总IgE水平分别为(92±37)KU/L、(122±45)KU/L和(146±44)KU/L,哮喘组血清总IgE水平分别为(179±40)KU/L、(294±51)KU/L和(341±80)KU/L;IL-13基因+1923C/T位点基因型CC、CT和TT在健康对照组中血清总IgE水平分别为(85±31)KU/L、(102±38)KU/L和(144±49)KU/L,哮喘组血清总IgE水平分别为(186±65)KU/L、(297±87)KU/L和(363±140)KU/L.在两基因位点中,相同基因型的血清总IgE水平比较,哮喘组高于对照组,差异有统计学意义(t值分别为4.653、6.547、7.754和4.673、6.784、8.157,均P<0.01).同组内的CT、TT基因型血清总IgE水平高于CC基因型,差异有统计学意义(t值分别为5.748和6.253,均P<0.01).结论 IL-4基因启动子区+33C/T和IL-13内含子+1923C/T多态性位点与哮喘易感性和血清总IgE浓度升高相关联.IL-4基因和IL-13基因是影响哮喘的重要候选基因.

abstractsObjective To investigate the correlation between the single nucleotide polymorphisms (SNP) of +33C/T in the promoter region of IL-4 gene and +1923C/T in intron-3 region of IL-13 gene and the susceptibility of asthma, and to study the impact of these polymorphisms upon total serum IgE levels. Methods The 2 polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), in 150 asthmatic subjects(asthma group)and 160 healthy controls (healthy control group) of the Han nationality in Shandong province enrolled from December 2003 to June 2007. The total serum IgE levels were determined by ELISA. Results The genotype frequencies of CC, CT and TT in + 33C/T sites of IL-4 gene were 43% (68/160), 35% (56/160), 22% (36/160) respectively in the controls, and 18% (27/150), 36% (54/150), 46% (69/150) respectively in the asthmatic subjects. The genotype frequencies of CC, CT and Tt in + 1923C/T sites of IL-13 gene were 41% (66/160), 43% (68/160), 16% (26/160) respectively in the controls, and 21% (31/150), 38% (57/150), 41% (61/150) respectively in the asthmatic subjects. The distribution of genotype in each sites between the 2 groups was significantly different (X2=27.821,26.544 respectively, all P <0.01). The CT and TT genotypes carried higher risks for asthma than CC genotypes (X2=21.870,14.206 respectively, all P<0.01). The total serum IgE levels of CC, CT and TT in + 33C/T sites of IL-4 gene were (92±37), (122±45), (146±44) KU/L respectively in the controls, and (179±40), (294±51), (341±80) KU/L respectively in the asthmatic subjects. The total serum IgE levels of CC, CT and TT in + 1923C/T sites of IL-13 gene were (85±31), (102±38), (144±49) KU/L respectively in the controls, and (186±65), (297±87), (363±140)KU/L respectively in the asthmatic subjects. In these 2 sites, the total serum IgE level of asthmatics was higher than that of the controls with the same genotype between the 2 groups (t= 4.653,6.547,7.754; and 4.673,6.784,8.157 respectively, all P <0.01). The total serum IgE levels of CT,TT genotypes were higher than CC genotypes in the same group (t=5.748, 6.253 respectively, all P < 0.01). Conclusions There was a significant correlation between the polymorphisms of + 33C/T sites of IL-4 and + 1923C/T sites of IL-13 gene and susceptibility to asthma and increase of the total serum IgE. The IL-4 gene and IL-13 gene may be important candidate genes for asthma.