Molecular Detection of the -308 G/A Polymorphism in the Tumor Necrosis Factor Alpha (TNFα) Gene Promoter and Its Relationship with the Development of Severe Dengue in Patients from Urabá Subregion, Antioquia-Colombia

Dengue fever is a viral infection caused by the dengue virus (DENV), a positive sense RNA virus belonging to Flaviviridae family. The virus is transmitted to humans through the bite of the Aedes aegypti mosquito. Worldwide, between 100 and 400 million cases are reported annually. The infection in humans can cause three clinical forms, which are related to severity: dengue without warnings signs, dengue with warnings signs, and severe dengue. Genetic variants in genes encoding immune system proteins have been associated with severe clinical forms of dengue, including variants in TNF-α. TNF-α plays a key role in dengue immunopathogenesis, and promoter polymorphisms may influence TNF-α expression and inflammatory responses associated with severe disease. Therefore, understanding host genetic variation may contribute to elucidating mechanisms involved in progression to severe clinical forms. This study explored the association between the TNF-α -308 G>A promoter polymorphism and dengue severity. We included 92 laboratory-confirmed dengue cases: 30 with dengue without warning signs, 43 with dengue with warning signs, and 19 with severe dengue. Genotyping was performed using PCR amplification, Sanger sequencing, and bioinformatic analysis of the TNF-α promoter region. Because of the low frequency of A allele carriers and sparse data, pairwise Firth penalized logistic regression models adjusted for age and primary/secondary infection status were used to evaluate the association between variant carrier status and dengue severity. The TNF-α -308 A allele was detected in a small proportion of participants, with variant carriers accounting for 10.5% of severe dengue cases. Adjusted analyses showed higher point estimates for severe dengue compared with dengue without warning signs and dengue with warning signs; however, the associations were not statistically significant, and confidence intervals were wide. Genotype frequencies showed no statistically significant deviation from Hardy–Weinberg equilibrium (p = 0.112), and the estimated post hoc statistical power was 11.3%. The TNF-α -308 G>A polymorphism was not significantly associated with dengue severity in this sample. The observed estimates were imprecise and should be considered exploratory, warranting confirmation in larger and more diverse populations.