Chuansumrit Ampaiwan, Anantasit Nattachai, Sasanakul Werasak, Chaiyaratana Wathanee, Tangnararatchakit Kanchana, Butthep Punnee, Chunhakan Sirichan, Yoksan Sutee
Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Paediatr Int Child Health. 2013 May;33(2):97-101. doi: 10.1179/2046905512Y.0000000049.
A single nucleotide polymorphism located at the promoter -308A of tumour necrosis factor-alpha (TNF-α) gene may affect transcription and increase cytokine production, leading to the severe manifestation of dengue virus infection.
To study the association of the TNF-α -308A allele and the severity of patients with dengue infection.
112 patients suspected of having dengue infection and 106 normal controls were enrolled in the study. Mean (SD) age was 10.4 (3.6) years. In all, 19 and 82 patients were diagnosed with dengue fever (DF) and dengue haemorrhagic fever (DHF), respectively, while 11 were diagnosed with other febrile illnesses (OFIs). They were tested for the polymorphisms at the promoter -308 position of the TNF-α gene and their TNF-α levels were measured.
In the patients with dengue infection (14/202, 6.9%) with OFIs (1/22, 4.5%) and in normal controls (17/212, 8.0%), the frequency of the TNF-α -308A allele was not significantly different. Moreover, no statistically significant difference was found in patients with various clinical manifestations of dengue infection involving DF (5.3%, 2/38), DHF grade I (5.0%, 2/40), DHF grade II (9.5%, 4/42), DHF grade III (2.5%, 1/40) and DHF grade IV (11.9%, 5/42). However, patients with dengue infection and significant bleeding manifestations, apart from petechiae and ecchymosis, tended to have a higher frequency of the TNF-α -308A allele (11.8%, 9/76) than those without significant bleeding manifestations (5/126, 4.0%) (P = 0.056). The levels of TNF-α were additionally measured in 67 patients but the results failed to demonstrate a functional effect in the transcriptional rate of the TNF-α -308A allele.
In patients with dengue infection there is an association between the TNF-α -308A allele and the risk of bleeding. The test may be used as one of the predictors of the severity of dengue infection.
肿瘤坏死因子-α（TNF-α）基因启动子-308A处的单核苷酸多态性可能影响转录并增加细胞因子的产生，导致登革病毒感染的严重表现。
研究TNF-α -308A等位基因与登革热感染患者严重程度之间的关联。
本研究纳入了112例疑似登革热感染患者和106例正常对照。平均（标准差）年龄为10.4（3.6）岁。其中，19例和82例患者分别被诊断为登革热（DF）和登革出血热（DHF），11例被诊断为其他发热性疾病（OFI）。对他们进行了TNF-α基因启动子-308位点的多态性检测，并测量了他们的TNF-α水平。
登革热感染患者（14/202，6.9%）、OFI患者（1/22，4.5%）和正常对照（17/212，8.0%）中，TNF-α -308A等位基因的频率无显著差异。此外，在登革热感染的各种临床表现患者中，包括DF（5.3%，2/38）、I级DHF（5.0%，2/40）、II级DHF（9.5%，4/42）、III级DHF（2.5%，1/40）和IV级DHF（11.9%，5/42），未发现统计学上的显著差异。然而，除瘀点和瘀斑外有明显出血表现的登革热感染患者，其TNF-α -308A等位基因频率（11.8%，9/76）往往高于无明显出血表现的患者（5/126，4.0%）（P = 0.056）。另外对67例患者测量了TNF-α水平，但结果未能证明TNF-α -308A等位基因转录率有功能效应。
在登革热感染患者中，TNF-α -308A等位基因与出血风险之间存在关联。该检测可作为登革热感染严重程度的预测指标之一。
