Human visceral leishmaniasis and polymorphisms in interleukin-coding genes: a systematic review

Area of Science:

• Immunogenetics
• Infectious Diseases
• Molecular Biology

Background:

• Visceral leishmaniasis (VL) is a severe neglected tropical disease caused by *Leishmania donovani* complex.
• Host genetic factors, particularly cytokine gene polymorphisms, are implicated in VL susceptibility and resistance.
• Understanding these genetic associations can reveal disease mechanisms and potential therapeutic targets.

Purpose of the Study:

• To systematically review and meta-analyze the association between single nucleotide polymorphisms (SNPs) in interleukin genes and clinical outcomes of VL.
• To identify specific cytokine gene polymorphisms that influence susceptibility or resistance to VL infection.

Main Methods:

• Systematic review and meta-analysis of studies from EMBASE, PubMed, Scopus, SciELO, and Web of Science.
• Two independent reviewers screened studies, extracted data, and assessed quality; a third reviewer resolved discrepancies.
• Statistical analysis using genetic models to calculate odds ratios (OR) and 95% confidence intervals (CIs) for associations.

Main Results:

• 28 articles were included in the systematic review, with 9 contributing to the meta-analysis.
• Significant associations were found between IFN-γ +874T/A polymorphisms (dominant and heterozygous models) and VL risk.
• IL-18 -137G/C polymorphism (recessive model) also showed a significant association with VL.
• No significant association was observed for IL-10 gene SNPs with VL.

Conclusions:

• Single nucleotide polymorphisms (SNPs) in the IFN-γ and IL-18 genes are associated with an increased risk of developing visceral leishmaniasis.
• These findings highlight the role of specific cytokine genetic variations in modulating host response to *Leishmania donovani* infection.
• Further research into these genetic associations could inform strategies for VL prevention and management.