TNF-α 308 (rs1800629) and INF-γ +874 polymorphisms in dengue progression: genotype-specific trends amidst allelic non-association in West Africa.

Abstract

Dengue, transmitted by Aedes mosquitoes, represents a significant global health challenge due to its complex host-pathogen interactions and varying disease severity. Genetic factors are known to influence the clinical outcome of dengue infections. This study aimed to investigate the potential role of TNF-α gene polymorphism 308 (rs1800629) and INF-γ +874 (rs62559044) in the progression of dengue virus infection. Conducted in the Central region of Burkina Faso, this study included 246 participants, comprising 117 controls and 129 dengue-positive patients. Genotyping of the TNF-α 308 (rs1800629) and INF-γ +874 A/T (rs62559044) polymorphisms was performed using restriction fragment length polymorphism (RFLP) and Amplification Refractory Mutation System PCR (ARMS-PCR) techniques, respectively.  Our analysis revealed no significant correlation between lymphocyte count and dengue severity (P = 0.95). Although we did not find an association between the alleles of the SNPs TNF-α 308 (rs1800629) and INF-γ +874 (rs6255904) studied with either DF or severe DS, we cannot conclude the same for their respective genotypes Thus, the AA and GG genotypes of TNF-α are associated with the contraction of DF and DS, respectively; the former is even associated with the progression of  DF to the severe form of the disease. For INF-γ  AA genotypes are more associated with progression to severe dengue and the AT heterozygote could be associated with a possibility of preventing progression to DS forms. . The A allele frequencies was higher frequency in DF than in DS pour TNF-α 308  , but this difference lacked statistical significance (P > 0.005). With INF-γ  tTT genotype was more prevalent in DS, whereas the AT genotype frequencies differed between DF (23.96%) and DS (19.35%). Our results reveal through the allelic levels of TNF-α 308 and INF-γ +874; that the latter would not play a significant role in the progression of dengue virus infection to severe forms. However, previous studies through a clear mechanism show a strong association between the concentrations of these cytokines and the pathogenesis of dengue. This underlines the need for further investigations to elucidate the genetic determinants of the severity of dengue. In particular, a proteomic study coupled with sequencing on a representative population of the West African region would be a great asset in understanding the involvement of the genes of these cytokines in the pathogenesis of dengue.