Tumour necrosis factor gene polymorphism in dengue infection: association with risk of bleeding

Background: A single nucleotide polymorphism located at the promoter -308A of tumour necrosis factor-alpha (TNF-alpha) gene may affect transcription and increase cytokine production, leading to the severe manifestation of dengue virus infection. Aim: To study the association of the TNF-alpha -308A allele and the severity of patients with dengue infection. Methods: 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-alpha gene and their TNF-alpha levels were measured. Results: 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-alpha -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-alpha -308A allele (11.8%, 9/76) than those without significant bleeding manifestations (5/126, 4.0%) (P=0.056). The levels of TNF-alpha were additionally measured in 67 patients but the results failed to demonstrate a functional effect in the transcriptional rate of the TNF-alpha -308A allele. Conclusion: In patients with dengue infection there is an association between the TNF-alpha -308A allele and the risk of bleeding. The test may be used as one of the predictors of the severity of dengue infection.