Department of Pediatrics, the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Gene. 2012 Feb 15;494(1):96-101. doi: 10.1016/j.gene.2011.09.027. Epub 2011 Nov 28.
The present study aims to investigate the association between the genetic polymorphisms of interferon (IFN)-γ and interleukin (IL)-4 with childhood susceptibility to asthma and the levels of IFN-γ, IL-4, and immunoglobulin (Ig) E among asthmatic children. A total of 100 asthmatic children and 122 control children were enrolled in the present study. The genotypes of the IFN-γ gene at the -179G/T locus and the IL-4 gene at the -33C/T and -589C/T loci were detected using polymerase chain reaction with restriction fragment length polymorphism. The IFN-γ gene at the +874A/T locus and the IFN-γ CA repeats were tested using allele-specific and capillary electrophoresis, respectively, whereas the IFN-γ, IL-4, and total IgE levels were measured using enzyme-linked immunosorbent assays. The 100 asthmatic children and the 122 control children were all GG homozygous in the -179 locus of the IFN-γ gene, which shows that the IFN-γ gene is not mutated at the -179 locus. No significant differences were found in terms of genotypic and allelic frequency distribution in the IFN-γ gene or the CA repeat at the +874A/T locus between the asthmatic children and the control (P>0.05). An association was found between the polymorphism of the IFN-γ gene at +874A/T and IFN-γ levels. IFN-γ expression was lower among patients with the AA genotype than those with the AT genotype (P<0.05); the genotypic and allelic frequency distributions of the IL-4 gene at -33C/T and -589C/T were significantly different between the asthmatic children and the control (P<0.05). The levels of IL-4 and IgE among children with TT genotype at the -33 and -589 loci were higher than those with the CT genotype, but only the polymorphism at -33C/T was associated with IL-4 levels (P<0.05). The polymorphisms of the IFN-γ gene at +874A/T or the CA repeats are not correlated with susceptibility to asthma. Thus, the polymorphism at +874A/T is correlated with IFN-γ level. The TT genotypes of the IL-4 gene at the -33 and -589 loci are associated with asthma susceptibility in children, and polymorphism at the -33 locus may be associated with IL-4 level.
本研究旨在探讨干扰素(IFN)-γ和白细胞介素(IL)-4的基因多态性与儿童哮喘易感性的关系,以及哮喘儿童 IFN-γ、IL-4 和免疫球蛋白(Ig)E 的水平。本研究共纳入 100 例哮喘儿童和 122 例对照儿童。采用聚合酶链反应-限制性片段长度多态性检测 IFN-γ基因-179G/T 位点、IL-4 基因-33C/T 和-589C/T 位点的基因型,采用等位基因特异性和毛细管电泳法检测 IFN-γ基因+874A/T 位点和 IFN-γ CA 重复,采用酶联免疫吸附试验检测 IFN-γ、IL-4 和总 IgE 水平。100 例哮喘儿童和 122 例对照儿童 IFN-γ 基因-179 位点均为 GG 纯合子,提示 IFN-γ 基因在-179 位点未发生突变。哮喘儿童与对照组 IFN-γ 基因和+874A/T 位点 CA 重复的基因型和等位基因频率分布无显著性差异(P>0.05)。IFN-γ 基因+874A/T 多态性与 IFN-γ 水平相关。AA 基因型患者 IFN-γ 表达低于 AT 基因型患者(P<0.05);哮喘儿童与对照组 IL-4 基因-33C/T 和-589C/T 基因型和等位基因频率分布差异有统计学意义(P<0.05)。-33 和-589 位点 TT 基因型患儿 IL-4 和 IgE 水平高于 CT 基因型患儿,但仅-33C/T 多态性与 IL-4 水平相关(P<0.05)。IFN-γ 基因+874A/T 或 CA 重复多态性与哮喘易感性无关。因此,+874A/T 多态性与 IFN-γ 水平相关。IL-4 基因-33 和-589 位点 TT 基因型与儿童哮喘易感性相关,-33 位点多态性可能与 IL-4 水平相关。