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肿瘤坏死因子-α启动子-308 G/A 多态性与早产儿早发性败血症的关系。

Association between Tumor Necrosis Factor-α Promoter -308 G/A Polymorphism and Early Onset Sepsis in Preterm Infants.

机构信息

Institute of Legal Medicine, Faculty of Medicine, University of Belgrade.

Institute of Neonatology.

出版信息

Tohoku J Exp Med. 2019 Apr;247(4):259-264. doi: 10.1620/tjem.247.259.

DOI:10.1620/tjem.247.259
PMID:31006736
Abstract

Early-onset neonatal sepsis (EOS) is diagnosed during the first 7 days of neonatal life and is the major cause of morbidity and mortality among preterm infants. Genetic predisposition may have an impact on EOS susceptibility and outcome. The aim of our study was to explore the association between TNF-α -308 G/A or IL-6 -174 G/C gene polymorphism and the susceptibility and outcome of EOS in preterm infants. The study included 471 preterm infants: 282 with EOS (151 with culture proven sepsis and 131 with clinical sepsis) and 189 without infection (control group). TNF-α -308 G/A and IL-6 -174 G/C were genotyped using Real-time RCR method. We observed significantly higher frequency of A allele of TNF-α -308 G/A polymorphism in blood culture proven EOS (p = 0.017) or clinical EOS (p = 0.025) compared with the control group. Logistic regression confirmed significant association between TNF-α -308 GA+AA genotypes and development of culture proven EOS (B = -0.718, p = 0.013) or clinical EOS (B = -0.602, p = 0.027). No significant differences in IL6 -174G/C alleles or genotypes distribution have been observed between culture proven EOS group, clinical EOS group and the control group. An association between TNF-α -308 G/A or IL-6 -174 G/C genotypes and EOS lethal outcome was not observed (p = 0.652 and p = 0.384, respectively). According to our analysis of large cohort of preterm infants with clearly defined EOS groups, the TNF-α -308 A allele may be a risk factor for the EOS occurrence.

摘要

早发型新生儿败血症 (EOS) 是在新生儿期的前 7 天内诊断出来的,是早产儿发病率和死亡率的主要原因。遗传易感性可能对 EOS 的易感性和结局有影响。我们的研究目的是探讨 TNF-α-308 G/A 或 IL-6-174 G/C 基因多态性与早产儿 EOS 易感性和结局的关系。该研究纳入了 471 例早产儿:282 例患有 EOS(151 例有培养证实的败血症和 131 例有临床败血症)和 189 例无感染(对照组)。采用实时 RCR 方法对 TNF-α-308 G/A 和 IL-6-174 G/C 进行基因分型。我们观察到血液培养证实的 EOS(p=0.017)或临床 EOS(p=0.025)患者 TNF-α-308 G/A 多态性的 A 等位基因频率明显更高。Logistic 回归证实 TNF-α-308 GA+AA 基因型与培养证实的 EOS(B=-0.718,p=0.013)或临床 EOS(B=-0.602,p=0.027)的发生有显著关联。在培养证实的 EOS 组、临床 EOS 组和对照组之间,IL6-174G/C 等位基因或基因型分布无显著差异。TNF-α-308 G/A 或 IL-6-174 G/C 基因型与 EOS 致死结局之间无关联(p=0.652 和 p=0.384)。根据我们对明确定义的 EOS 组的大队列早产儿的分析,TNF-α-308 A 等位基因可能是 EOS 发生的危险因素。

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