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FLI1 polymorphism affects susceptibility to cutaneous leishmaniasis in Brazil
L Castellucci1, S E Jamieson, E N Miller
1Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Brazil.
Genes and Immunity
|June 3, 2011
Summary
The FLI1 gene influences resistance to cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). Genetic variations in FLI1 are linked to disease susceptibility, suggesting FLI1 as a potential therapeutic target for leishmaniasis and wound healing.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) are significant global health concerns.
- Murine studies identified Fli1 as a gene influencing leishmaniasis resistance and wound healing.
Purpose of the Study:
- To investigate the role of the FLI1 gene in human CL and ML caused by Leishmania braziliensis.
- To analyze single nucleotide polymorphisms (SNPs) in FLI1 regulatory regions for disease association.
Main Methods:
- Analysis of intron 1 SNPs in FLI1 within nuclear families affected by CL and ML.
- Case-pseudocontrol logistic regression and haplotype analysis were employed.
- Replication of findings in an independent cohort.
Main Results:
- A significant association was found between allele C of FLI1_rs7930515 and CL susceptibility in both primary and replication cohorts.
- FLI1_rs7930515 is in linkage disequilibrium with a functional microsatellite in the promoter region.
- Distinct haplotype associations were observed for ML compared to CL.
Conclusions:
- FLI1 is a genetic factor influencing susceptibility to human CL and ML.
- The findings highlight the importance of wound healing in CL pathogenesis.
- Modulating FLI1 presents a potential therapeutic strategy for leishmaniasis.
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