新生儿细菌性脑膜炎与TLR2/9基因多态性的关系

Relationship between neonatal bacterial meningitis and TLR2/9 gene polymorphism

目的探讨新生儿细菌性脑膜炎(BM)感染Toll样受体2/9(Toll like receptor 2/9,TLR2/9)基因多态性。方法选择南通市妇幼保健院儿内科2018年9月-2020年8月收治的BM新生儿75例作为BM组,选择同期医院出生的健康新生儿80例作为对照组,留取两组新生儿脐带血标本,提取全血DNA后,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)检测两组患儿外周血中TLR2基因rs5743708位点和TLR9基因rs352140位点基因型分布,比较不同基因型BM发病时间及预后。结果BM组患儿TLR2基因rs5743708位点AA基因型频率、A等位基因频率(16.00%、36.67%)及TLR9基因rs352140位点TT基因型、T等位基因频率(24.00%、41.33%)高于对照组,CC基因型频率(41.33%)低于对照组(P<0.05);校正性别、出生时孕周、出生时体质量等因素后,Logistic回归分析结果显示,携带TLR2基因rs5743708位点AA基因型、A等位基因以及TLR9基因rs352140位点TT基因型、T等位基因是新生儿发生BM的影响因素(P<0.05);TLR2基因rs5743708位点和TLR9基因rs352140位点不同基因型BM患儿发病时间及预后比较分布无统计学意义。结论TLR2基因rs5743708位点和TLR9基因rs352140位点基因多态性与本地区新生儿对BM易感性有关,其中TLR2基因rs5743708位点A等位基因和TLR9基因rs352140位点T等位基因为易感基因。

OBJECTIVE To investigate Toll like receptor 2/9(Toll like receptor 2/9,TLR^(2)/9)gene polymorphism in neonatal bacterial meningitis(BM)infection.METHODS Totally 75 cases of BM newborns admitted to the Department of Pediatrics of Nantong Maternal and Child Health Hospital from September 2018 to August 2020 were selected as the BM group,and 80 healthy newborns born in the hospital during the same period were selected as the control group,and the umbilical cord blood of the two groups of newborns was collected.After the DNA of whole blood was extracted,restriction fragment length polymorphism polymerase chain reaction(PCR-RFLP)was used to detect the genotype distribution of TLR^(2) gene rs5743708 and TLR9 gene rs352140 in the peripheral blood of the two groups of children,and the onset time and prognosis of BM with different genotype was compared.RESULTS The AA genotype frequency,A allele frequency(16.00%,36.67%)of the TLR^(2) gene rs5743708 site,and the TT genotype and T allele frequency(24.00%,41.33%)of the TLR9 gene rs352140 site in the BM group were significantly higher than those in the control group,the CC genotype frequency(41.33%)was significantly lower than that in the control group(P<0.05).After adjusting for factors such as gender,gestational age at birth,body weight at birth,the logistic regression analysis showed that the AA genotype,A allele at locus rs5743708 of the TLR^(2) gene,and the TT genotype and T allele at locus rs352140 of the TLR9 gene were the influencing factors of neonatal BM(P<0.05).There was no significant difference in the onset time and prognosis of children with different genotypes distribution at the rs5743708 locus of TLR^(2) gene and rs352140 locus of TLR9 gene.CONCLUSION The genetic polymorphisms at the rs5743708 locus of the TLR^(2) gene and the rs352140 locus of the TLR9 gene were related to the susceptibility of newborns to BM in this area.Among them,the A allele at the rs5743708 locus of the TLR^(2) gene and the T allele at the rs352140 locus of the TLR9 gene were susceptible genes.