Infectious Diseases Clinic, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gh. Marinescu St, 540139, Targu Mures, Romania.
Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gh. Marinescu St, 540139, Targu Mures, Romania.
BMC Infect Dis. 2020 Mar 14;20(1):221. doi: 10.1186/s12879-020-4910-6.
The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome.
We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset.
TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock.
TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.
本研究旨在评估肿瘤坏死因子-α（TNF-α）遗传变异作为脓毒症生物标志物的潜在作用。具体而言，我们旨在确定 TNF-α 基因的单核苷酸多态性（SNP）是否与脓毒症的风险、严重程度和结局有关。
我们对 163 名成年危重症脓毒症患者（脓毒性休克 65 例，脓毒症 98 例，进一步分为 40 例存活者和 123 例死亡者）和 232 名健康对照者进行了前瞻性研究。对所有患者和对照者进行 TNF-α SNP（-308G/A、-238G/A、-376G/A 和+489G/A）的基因分型，并在脓毒症发病后 24 小时内测量血浆细胞因子水平。
TNF-α+489G/A A-等位基因携带与发生脓毒症和脓毒性休克的风险显著降低相关（AA+AG 与 GG：OR=0.53；p=0.004；95%CI=0.34-0.82 和 OR=0.39；p=0.003；95%CI=0.21-0.74），但与脓毒症相关结局无关。其他 TNF-α 启动子 SNP 或其单倍型频率与脓毒症或脓毒性休克风险之间均无显著相关性。TNF-α 水平在脓毒性休克中较高；它们与 SNP 基因型分布无关；每种多态性的 GG 纯合性与脓毒性休克中更高的 TNF-α水平相关。
TNF-α+489G/A SNP A-等位基因携带可能对脓毒症和脓毒性休克的发生具有保护作用，但显然不会影响脓毒症相关死亡率。启动子 TNF-α SNP 不影响转录，与不同的脓毒症、脓毒性休克风险或结局无关。
