NLR TLR7基因多态性与肠道病毒感染患儿预后及临床表型的相关性

Association of NLR and TLR7 gene polymorphisms with prognosis and clinical phenotype caused by enterovirus infection

目的 探讨中性粒细胞/淋巴细胞(NLR)及Toll样受体7(TLR7)基因单核苷酸多态性(SNP)与肠道病毒感染患儿不同临床表型及不同感染型别的相关性。方法 应用巢式RT-PCR进行肠道病毒分型;TapMan探针基因分型技术,对200例感染者和100名健康对照TLR7基因rs3853839位点进行基因分型,比较其等位基因频率的差异;检测相关SNP位点不同基因型携带与不同临床表型的相关性。结果 测序分析分型:EV71型8.5%(17/200)、CoxA16型17.5%(35/200)、CoxA6型28.5%(57/200)、CoxA10型22.0%(44/200),其他肠道病毒型23.5%(47/200);EV71感染者rs3853839基因型GC和CC的频率明显高于其他型别感染组(P<0.05);脑炎/无菌性脑膜炎组rs3853839基因型C的频率也明显高于其他症状组(P<0.05);重症组患儿NLR高于轻症组(P<0.05),NLR升高与疾病严重程度显著相关。回归分析确定NLR升高(HR=2.46,95%CI为1.99~4.669)。结论 TLR7基因rs3853839等位基因C是儿童EV71感染的危险因素并且与临床症状重症化相关;NLR异常作为肠道病毒感染患者不良临床预后的独立生物标志物。

Objective To investigate the relationship between neutrophil/lymphocyte(NLR), single nucleotide polymorphism(SNP) of Toll-like receptor 7 gene and different clinical phenotypes, types of enterovirus infection.Methods Nested RT-PCR was used for enterovirus typing.TapMan probe genotyping technology was used to genotype the rs3853839 locus of TLR7 gene in 200 infected persons and 100 healthy controls.The difference of allele frequency was compared.Detect the correlation between different genotypes of related SNP loci and different clinical phenotypes.Results EV71 8.5%(17/200), CoxA16 17.5%(35/200), CoxA6 28.5%(57/200), CoxA10 22.0%(44/200), other enterovirus 23.5%(47/200).The frequency of GC and CC of rs3853839 genotype in EV71 infected group was significantly higher than that in other types of infection group(P<0.05).The frequency of rs3853839 genotype C in encephalitis/aseptic meningitis group was also significantly higher than that in other symptom groups(P<0.05).The NLR results of children in the severe group was higher than that in the mild group(P<0.05).The increase of NLR was significantly related to the severity of the disease.Regression analysis determined that the NLR increased(HR=2.46, 95%CI:1.99-4.669).Conclusion TLR7 rs3853839 allele C is a risk factor for EV71 infection in children, and the frequency of allele C is associated with the severity of clinical symptoms.Abnormal NLR as an independent biomarker of poor clinical prognosis in patients with enterovirus infection.