Host genetics and dengue fever

Area of Science:

• * Infectious Diseases
• * Human Genetics
• * Immunology

Background:

• * Dengue fever, a significant global health issue in tropical and subtropical regions, presents with varying severity from asymptomatic to life-threatening.
• * Host genetic factors, particularly patient genetic profiles, play a critical role in determining dengue disease severity.
• * While African ancestry has been linked to protection against severe dengue in outbreak regions, the precise genetic mechanisms remain under investigation.

Purpose of the Study:

• * To review and synthesize findings from genetic association studies investigating the relationship between host genetics and dengue outcomes.
• * To highlight the need for meta-analyses to resolve controversial results and establish consensus on genetic factors influencing severe dengue.
• * To emphasize the importance of understanding the interplay between viral, host genetic, and immunological factors for effective dengue prevention and treatment.

Main Methods:

• * Review of published association studies, including candidate gene approaches (e.g., HLA, cytokine genes) and Genome-Wide Association Studies (GWAS).
• * Analysis of Single Nucleotide Polymorphisms (SNPs) associated with dengue risk or protection.
• * Identification of studies examining genetic polymorphisms in relation to dengue severity across diverse populations.

Main Results:

• * Numerous genetic polymorphisms in genes such as MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10, and PLCE1 have been associated with dengue risk or protection.
• * GWAS identified novel SNPs linked to African ethnicity that were not previously found in candidate gene studies.
• * Replication of findings across different populations suggests the involvement of specific genetic variants in dengue pathogenesis, although results are often controversial.

Conclusions:

• * Host genetics are a critical determinant of dengue disease severity, with specific gene variants influencing susceptibility and protection.
• * Further meta-analyses are required to consolidate evidence and resolve discrepancies in current genetic association studies.
• * A comprehensive understanding of the complex interactions between dengue virus, host genetics, and the immune system is essential for developing effective interventions.