TLR4基因多态性与小儿反复呼吸道感染的关系

Association of Toll-like receptor 4 gene polymorphism with recurrent respiratory tract infection in children

目的探究Toll样受体4(TLR4)基因多态性与小儿反复呼吸道感染(RRTI)的关系。方法选择107例RRTI病儿作为观察组,另选103例体检健康儿童作为对照组(近1年未出现RRTI),采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术分析两组TLR4基因rs2737190位点多态性,比较不同病情严重程度病儿TLR4基因多态性的差异,并分析不同TLR4基因多态性病儿临床特征的差异。结果观察组TLR4基因rs2737190位点AG基因型、G等位基因频率均明显高于对照组,AA基因型频率明显低于对照组(χ^(2)=4.129~8.564,P<0.05);中重度RRTI病儿GG基因型、G等位基因频率明显高于轻度病儿,AA基因型频率显著低于轻度病儿(χ^(2)=9.233~13.357,P<0.05);AA基因型病儿年发作次数、合并呼吸困难比例,以及C反应蛋白、白细胞介素-6、γ-干扰素和丙二醛等指标均显著低于AG和GG基因型病儿,超氧化物歧化酶则显著高于AG和GG基因型病儿(χ^(2)=7.573,F=4.668~24.317,P<0.05)。结论TLR4基因rs2737190位点AG基因型、G等位基因频率会增加小儿RRTI易感性,并促进其炎症反应升高和病情进展。

Objective To investigate the association of Toll-like receptor 4(TLR4)gene polymorphism with recurrent respiratory tract infection(RRTI)in children.Methods A total of 107 children with RRTI were enrolled as RRTI group,and 103 children who underwent physical examination and did not experience RRTI in the past year were enrolled control group.Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the rs2737190 polymorphism of the TLR4 gene in each group.TLR4 gene polymorphism was compared between children with different severities,and clinical features were compared between children with different TLR4 gene polymorphisms.Results Compared with the control group,the observation group had significantly higher frequencies of AG genotype and G allele and a significantly lower frequency of AA genotype at TLR4 rs2737190 locus(χ^(2)=4.129-8.564,P<0.05).Compared with the children with mild RRTI,the children with moderate-to-severe RRTI had significantly higher frequencies of GG genotype and G allele and a significantly lower frequency of AA genotype(χ^(2)=9.233-13.357,P<0.05).Compared with the children with AG genotype or GG genotype,the children with AA genotype had significantly lower number of annual attacks and proportion of children with dyspnea,significantly lower serum levels of C-reactive protein,interleukin-6,interferon-γ,and malondialdehyde,and a significantly higher level of superoxide dismutase(χ^(2)=7.573,F=4.668-24.317,P<0.05).Conclusion The frequency of AG genotype and G allele at TLR4 rs2737190 locus may increase the susceptibility to RRTI and promote inflammation response and disease progression in children.