The Genetic Variant TNFA (rs361525) Is Associated with Increased Susceptibility to Developing Dengue Symptoms

Abstract

Dengue virus (DENV) is the causal agent of dengue fever. The symptoms and signs of dengue vary from febrile illness to hemorrhagic syndrome. IFITM3 and TNFA are genes of the innate immune system. Variants IFITM3 (rs12252 T>C) and TNFA (rs1800629 G > A and rs361525 G>A) might alter gene expression and change the course of the disease. Our first objective was to determine whether these variants were associated with the susceptibility and severity of dengue. The second was to assess the association of these variants with each symptom. We studied 272 cases with suspected dengue infection, of which 102 were confirmed dengue cases (DENV+) and 170 were dengue-like cases without DENV infection (DENV−). Samples of 201 individuals from the general population of Mexico were included as a reference. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique. Odds ratios and confidence intervals were calculated using Pearson's chi-square test and later adjusted for age and sex with a binary logistic regression model. Haldane correction is applied when necessary. We found a significantly higher frequency of the A allele of TNFA rs361525 in both the DENV+ and DENV− groups compared with the general population. Focusing on DENV+ and DENV−, the frequency of the A allele of TNFA rs361525 was higher in the DENV+ group. A broad spectrum of symptoms was related to the A allele of both TNFA variants. We conclude that TNFA rs361525 increases the susceptibility to symptomatic dengue but can also be associated with susceptibility to other dengue-like symptoms from unknown causes.