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新生儿中Toll样受体2、3、4和9基因多态性与重型肝炎易感性及预后的相关性

Correlation between TLR2, TLR3, TLR4, and TLR9 polymorphisms and susceptibility to and prognosis of severe hepatitis among the newborns.

作者信息

Qiu Xiao, Dong Yubin, Cao Yaqin, Luo Yingmei

机构信息

Department of Neonatal Intensive Care Unit, The Central Hospital of Zhoukou City, Zhoukou, Henan Province, China.

出版信息

J Clin Lab Anal. 2018 Mar;32(3). doi: 10.1002/jcla.22292. Epub 2017 Jul 13.

Abstract

BACKGROUND

This study was aimed to explore how toll-like receptor 2 (TLR2), TLR3, TLR4 and TLR9 influenced the risk and prognosis of severe hepatitis among the Chinese newborns.

METHODS

Altogether 135 newborns diagnosed with severe hepatitis and 140 healthy newborns were included in this study. Totally 12 single nucleotide polymorphisms (SNPs) within TLR2, TLR3, TLR4, and TLR9 were chosen and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. The univariate and multivariate analyses were used to analyze independent factors for prognosis of severe hepatitis among the Chinese newborns.

RESULTS

The SNPs within TLR2 [ie, rs1898830 (A>G) and rs3804100 (T>C)], TLR3 [ie, rs1879026 (G>T)], TLR4 [ie, rs2149356 (T>G)], and TLR9 [ie, rs187084 (T>C), rs352139 (A>G), and rs352140 (C>T)] were significantly associated with modified risk of neonatal severe hepatitis (all P<.05). Furthermore, rs1898830, rs1879026, rs187084 and rs352139 were also demonstrated to modulate the prognosis [ie, aspartate aminotransferase (AST)/alanine transaminase (ALT)>1.5] of newborns with severe hepatitis (all P<.05). Interestingly, the haplotype A-C-G-G-C-A-T were associated with higher susceptibility to neonatal severe hepatitis, and the newborns carrying haplotype A-C-G-G-C-A-T appeared to be correlated with more favorable prognosis (all P<.05).

CONCLUSIONS

Certain SNPs and haplotypes within TLR2, TLR3, TLR4, and TLR9 can be considered as the potentially treatment targets for neonatal severe hepatitis.

摘要

背景

本研究旨在探讨Toll样受体2(TLR2)、TLR3、TLR4和TLR9如何影响中国新生儿重症肝炎的风险和预后。

方法

本研究纳入了135例诊断为重症肝炎的新生儿和140例健康新生儿。选取TLR2、TLR3、TLR4和TLR9内共12个单核苷酸多态性(SNP),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)进行基因分型。使用逻辑回归计算比值比(OR)和95%置信区间(CI)。采用单因素和多因素分析来分析中国新生儿重症肝炎预后的独立因素。

结果

TLR2内的SNP[即rs1898830(A>G)和rs3804100(T>C)]、TLR3内的SNP[即rs1879026(G>T)]、TLR4内的SNP[即rs2149356(T>G)]以及TLR9内的SNP[即rs187084(T>C)、rs352139(A>G)和rs352140(C>T)]与新生儿重症肝炎的修正风险显著相关(所有P<0.05)。此外,rs1898830、rs1879026、rs187084和rs352139也被证明可调节重症肝炎新生儿的预后[即天冬氨酸转氨酶(AST)/丙氨酸转氨酶(ALT)>1.5](所有P<0.05)。有趣的是,单倍型A-C-G-G-C-A-T与新生儿重症肝炎的易感性较高相关,携带单倍型A-C-G-G-C-A-T的新生儿似乎与更有利的预后相关(所有P<0.05)。

结论

TLR2、TLR3、TLR4和TLR9内的某些SNP和单倍型可被视为新生儿重症肝炎的潜在治疗靶点。

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