State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, P. R, China.
School of Public Health, Peking University, Beijing, P. R, China.
PLoS Negl Trop Dis. 2018 Jun 25;12(6):e0006547. doi: 10.1371/journal.pntd.0006547. eCollection 2018 Jun.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus, SFTSV. We assessed whether the single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-α) were associated with risk to severity of SFTS. Five TNF-α SNPs (SNP1: T-1031C; SNP2: C-863A; SNP3: C-857T; SNP4: G-308A; SNP5: G-238A) were genotyped in 987 hospitalized SFTS patients and 633 asymptomatic/mild SFTSV-infected subjects of Chinese Han origin. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). The hospitalized SFTS patients had significantly lower frequency of G-238A A allele than those with mild/asymptomatic infection (P = 0.006). Furthermore, T-1031C C allele (P < 0.001) and G-238A A allele (P < 0.001) were significantly associated with decreased risk of death. Multiple haplotypes were significantly associated with decreased risk of SFTS hospital admission (SNP1-2, CC; SNP1-3, CCC; SNP1-4, CCCG; SNP1-5, CCCGA; SNP2-4, CCGA; SNP3-5, CGA; SNP4-5, GA) and death (SNP1-2, CA; SNP1-3, CAG; SNP1-4, CACG; SNP1-5, CACGG; SNP2-3, AC; SNP2-4, ACG; SNP2-5, ACGG) after correction for multiple comparisons. By using the ELISA assay, we observed that TNF-α concentration of hospitalized patients was significantly increased in acute phase than in convalescent phase (P < 0.001). Elevated TNF-α concentration was also revealed from fatal patients (P < 0.001). The -238A allele was associated with decreased serum TNF-α levels in SFTS patients in acute phase (P = 0.01). Our findings suggest that polymorphisms in TNF-α gene may play a role in mediating the risk to disease severity of SFTS in Chinese Han population.
严重发热伴血小板减少综合征（SFTS）是一种由新型布尼亚病毒引起的新发传染病。我们评估了肿瘤坏死因子-α（TNF-α）中的单核苷酸多态性（SNP）是否与 SFTS 的严重程度相关。对 987 例住院 SFTS 患者和 633 例无症状/轻度 SFTSV 感染的汉族人群进行了 5 个 TNF-αSNP（SNP1：T-1031C；SNP2：C-863A；SNP3：C-857T；SNP4：G-308A；SNP5：G-238A）的基因分型。采用多变量逻辑回归分析计算调整后的比值比（OR）和 95%置信区间（95%CI）。与轻度/无症状感染相比，住院 SFTS 患者的 G-238A A 等位基因频率显著降低（P = 0.006）。此外，T-1031C C 等位基因（P < 0.001）和 G-238A A 等位基因（P < 0.001）与死亡风险降低显著相关。多个单倍型与 SFTS 住院（SNP1-2，CC；SNP1-3，CCC；SNP1-4，CCCG；SNP1-5，CCCG；SNP2-4，CCGA；SNP3-5，CGA；SNP4-5，GA）和死亡（SNP1-2，CA；SNP1-3，CAG；SNP1-4，CACG；SNP1-5，CACGG；SNP2-3，AC；SNP2-4，ACG；SNP2-5，ACGG）显著相关，经多重比较校正后。通过 ELISA 检测，我们发现急性期住院患者 TNF-α浓度明显高于恢复期（P < 0.001）。死亡患者也显示出 TNF-α浓度升高（P < 0.001）。-238A 等位基因与 SFTS 患者急性期血清 TNF-α水平降低相关（P = 0.01）。我们的研究结果表明，TNF-α基因多态性可能在介导汉族人群 SFTS 严重程度的风险中起作用。
