Zhang Jialin, Chen Hong, Hu Liangping, Fu Jin, Zhang Huiqin, Chen Yuzhi
Asthma Center, Capital Institute of Pediatrics, Beijing 100020, China.
Zhonghua Yi Xue Za Zhi. 2002 Jan 25;82(2):114-8.
To investigate the correlation between the polymorphism of IL-4 and IL-10 gene promoters and the susceptibility of Chinese children to asthma and to study the impact of such polymorphism upon cytokine production.
The data of medical history, pulmonary function, hypersensitive test, and serum IgE were recorded among 168 unrelated Chinese children with asthma aged 5 approximately 15. Four polymorphism sites of IL-4 and IL-10 gen promoter regions were determined by PCR/RFLP. The peripheral blood monocyte (PBMC) was cultured and stimulated by lipopolysacchride (LPS). Then the contents of IL-4 and IL-10 gene promoter regions were determined by ELISA. 53 age-matched children without asthma were used as control.
(1) The allele frequencies of-598 (C/T) site of IL-4 gene promoter was significantly different between Chinese children and children of Caucasian and Afro-American origin (P = 0.01). The allele frequency of -1082 (G/A) site, -819 (C/T) site, and -592 (A/C) site in IL-10 gene promoter was significantly different between Chinese children and their British counterparts (P = 0.01). (2) The serum total IgE level was significantly different among children with different allelic sites in IL-4 and IL-10 gene promoters. A allele in IL-10 - 1082 (G/A) site and T allele in IL-10 - 819 (C/T) site -1082 were associated with elevated total serum IgE (P < 0.01, OR = 3.16; P < 0.05, OR = 1.84). (3) The IL-10 level in the supernatant of PBMC culture of children with homozygous genotypes of -819 TT and ATA/ATA in IL-10 gene promoter after stimulation of LPS was the lowest in comparison with those in the supernatant of PBMC culture of children with other genotypes (all P < 0.05). (4) No correlation was found between -589 (C/T) site in IL-4 gene promoter and asthma. There was no significant difference between the increase of IL-4 level in the supernatant of PBMC culture of children with the two different homozygous genotypes of IL-4 gene promoter.
(1) There is no significant correlation between the polymorphism sites in IL-4 and IL-10 gene promoters and the susceptibility to asthma among Chinese. (2) The polymorphism of IL-10 gene promoter may be an important candidate gene for severity of asthma. The allele -819T plays an important role in increase of the total serum IgE by reducing the upregulation of IL-10 gene expression.
探讨白细胞介素-4（IL-4）和白细胞介素-10（IL-10）基因启动子多态性与中国儿童哮喘易感性的关系，并研究这种多态性对细胞因子产生的影响。
记录168名年龄在5至15岁的无亲缘关系的中国哮喘儿童的病史、肺功能、过敏试验及血清免疫球蛋白E（IgE）数据。采用聚合酶链反应/限制性片段长度多态性（PCR/RFLP）方法检测IL-4和IL-10基因启动子区域的4个多态性位点。外周血单核细胞（PBMC）用脂多糖（LPS）培养和刺激，然后用酶联免疫吸附测定（ELISA）法检测IL-4和IL-10基因启动子区域的含量。选取53名年龄匹配的无哮喘儿童作为对照。
（1）IL-4基因启动子-598（C/T）位点的等位基因频率在中国儿童与白种人和非裔美国儿童之间有显著差异（P = 0.01）。IL-10基因启动子-1082（G/A）位点、-819（C/T）位点和-592（A/C）位点的等位基因频率在中国儿童与其英国同龄人之间有显著差异（P = 0.01）。（2）IL-4和IL-10基因启动子不同等位基因位点的儿童血清总IgE水平有显著差异。IL-10 -1082（G/A）位点的A等位基因和IL-10 -819（C/T）位点的T等位基因与血清总IgE升高有关（P < 0.01，比值比（OR）= 3.16；P < 0.05，OR = 1.84）。（3）LPS刺激后，IL-10基因启动子纯合基因型-819 TT和ATA/ATA的儿童PBMC培养上清液中IL-10水平与其他基因型儿童PBMC培养上清液中的IL-10水平相比最低（均P < 0.05）。（4）IL-4基因启动子-589（C/T）位点与哮喘无相关性。IL-4基因启动子两种不同纯合基因型的儿童PBMC培养上清液中IL-4水平升高无显著差异。
（1）IL-4和IL-10基因启动子多态性位点与中国人哮喘易感性无显著相关性。（2）IL-10基因启动子多态性可能是哮喘严重程度的重要候选基因。-819T等位基因通过降低IL-10基因表达上调而在血清总IgE升高方面起重要作用。
