ABSTRACT
Objectives
The outcomes of tegumentary leishmaniasis (TL) rely on a complex interaction between the host immune system and the parasite. This study assessed the influence of polymorphisms in immune-related genes on TL.
Methods
Web of Science, Scopus, PubMed, and Embase databases were searched systemically. The meta-analysis used a retrospective model in examining alleles, heterozygotes, and homozygotes. A quality assessment and an analysis of cumulative evidence were performed.
Results
A total of 29 genes (encoding for cytokines, chemokines, and other immune receptors) and 84 polymorphisms were analyzed. The IL-1β_rs16944 (OR = 1.341, p = 0.003), TNF-α_rs1800629 (OR = 3.804, p = 0.004), MIF_rs755622 (OR = 3.357, p = 0.001), and INF- γ_rs243056 (OR = 1.670, p = 0.028) polymorphisms were speculated as risk factor for TL. They decrease the expression of the corresponding genes crucial for TL control. The quality assessment score was approximately 50%, suggesting the need for a clear method and polymorphism characterization for further comparison. The relevant risk of bias and other considerations resulted in low and moderate cumulative evidence confidence.
Conclusions
IL-1β_rs16944, TNF-α_rs1800629, MIF_rs755622, and INF-γ_rs2430561 polymorphisms were speculated as risk factor for TL, corroborating that IL-1β, TNF-α, INF-γ, and MIF are involved in the TL pathogenesis.
Article highlights
Polymorphism in immune-related genes influences the outcomes of tegumentary leishmaniasis .
This systematic review evaluated 29 genes (encoding for cytokines, chemokines, and other immune receptors) and 84 polymorphisms.
According to meta-analysis, IL-1β_rs16944, TNF-α_rs1800629, MIF_rs755622, and INF-γ_rs2430561 polymorphisms are risk factors for tegumentary leishmaniasis.
The probable mechanism involves the downregulation of the expression of the corresponding genes by IL-1β_rs16944, TNF-α_rs1800629, MIF_rs755622, and INF-γ_rs2430561.
IL-1β, TNF-α, INF-γ, and MIF are involved in the pathogenesis of tegumentary leishmaniasis.
Declaration of interest
The funding sources had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. AAB, TSS, and JO have received a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES). LFO has received a fellowship from Fundação Araucária – Brazil. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
DSSLLN contributed to the design, search, screening, data extraction, data analysis, data interpretation, production of the figures, GRADE analysis, and writing of the report. FLO contributed to the search, screening, and data extraction. AAB contributed to the search, screening, data extraction, and quality assessment. TS contributed to the search, screening, data extraction, and meta-analysis. JO, ACFHRM, MVCL, and MSTM contributed to data validation, data interpretation and writing of the report. IGD and QALN contributed to data interpretation and writing of the report. IGD and TS contributed to the GRADE analysis. JJVT and MVCL contributed to design, data interpretation, meta-analysis, and writing of the report.
Data availability statement
The data that support the findings of this analysis are available from DSSLLN upon reasonable request.