MMP1及TIMP1基因多态性与儿童反复呼吸道感染的关联性

Association of polymorphisms of MMP1 and TIMP1 genes with recurrent respiratory tract infection in children

  • 摘要: 目的 探究反复呼吸道感染(RRTI)风险和疾病发展与基质金属蛋白酶1(MMP1)、组织金属蛋白酶抑制物1(TIMP1)基因多态性的关系。方法 选取2016年5月-2019年12月朝阳市中心医院确诊为RRTI患儿82例和同期体检健康儿童60名作为研究对象,采用聚合酶链式反应和限制性片段长度多态性技术,检测MMP1(-1607位点)、TIMP1(-372位点)基因多态性,分析不同基因型与RRTI的关系;采用酶联免疫吸附法检测外周血MMP1、TIMP1,分析血清MMP1、TIMP1对RRTI的预测价值。结果 存在被动吸烟、挑食和服用抗生素>7次/年是RRTI的独立危险因素(P<0.05);RRTI组MMP1、TIMP1高于对照组(P<0.05);受试者工作特征(ROC)分析显示,血清MMP1、TIMP1的曲线下面积(AUC)分别为0.766(95%CI为0.686~0.846)、0.784(95%CI为0.704~0.863);两组MMP1(-1607位点)基因型分布的比较,差异具有统计学意义(P<0.05),与对照组比较,RRTI组MMP1(-1607位点)2G等位基因频率明显升高(P<0.05);两组TIMP1(-372位点)基因型分布的比较,差异无统计学意义,但与对照组比较,RRTI组TIMP1(-372位点)C等位基因频率明显升高(P<0.05)。结论 MMP1(-1607位点)2G等位基因、TIMP1(-372位点)C等位基因是RRTI的危险因素,且被动吸烟、挑食和服用抗生素均会增加RRTI风险,临床应给予针对性管理措施,积极防控RRTI。

     

    Abstract: OBJECTIVE To explore the relationship between the risk of recurrent respiratory tract infection(RRTI) and the disease development and polymorphisms of matrix metalloproteinase-1(MMP1) and tissue inhibitor of metalloproteinase-1(TIMP1) genes. METHODS During the period from May 2016 to Dec 2019, 82 children with RRTI and 60 healthy children who underwent physical examination in Chaoyang Central Hospital were enrolled. The polymorphisms of MMP1(-1607 locus) and TIMP1(-372 locus) genes were detected by polymerase chain reaction-restriction fragment length polymorphism, and the relationship between different genotypes and RRTI was analyzed. The peripheral blood levels of MMP1 and TIMP1 were detected by enzyme-linked immunosorbent assay. The predictive value of serum MMP1 and TIMP1 for RRTI was analyzed. RESULTS Passive smoking, picky eater and taking antibiotics more than 7 times/year were the independent risk factors for RRTI(P<0.05). MMP1 and TIMP1 levels in the RRTI group were significantly higher than those in the control group(P<0.05). The receiver operating characteristic(ROC) curves analysis showed that area under the ROC curve(AUC) values of serum MMP1 and TIMP1 levesls were 0.766(95% confidence interval: 0.686-0.846) and 0.784(95% confidence interval: 0.704-0.863), respectively. There were significant differences in the distribution of MMP1 genotype(-1607 locus) between the two groups(P<0.05). Compared with control group, the frequency of 2 G allele at MMP1(-1607 locus) in the RRTI group was significantly increased(P<0.05). There was no significant difference in the distribution of TIMP1(-372 locus) genotype between the two groups; while compared with control group, the frequency of C allele at TIMP1(-372 locus) in the RRTI group was significant higher(P<0.05). CONCLUSION 2 G allele at MMP1(-1607 locus) and C allele at TIMP1(-372 locus) are risk factors of RRTI. The passive smoking, picky eating and taking antibiotics will increase the risk of RRTI. Clinically, targeted management measures should be performed to prevent RRTI effectively.

     

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