Last Updated: 03/12/2025
Study of single base polymorphisms (SNPs) in the promoter region of the TGF-1 and IL-1 cytokine genes associated with malaria and asymptomatic infection by Plasmodium spp. in the Rio Negro region, Amazonas, Brazil.
Objectives
*Original title in Portuguese: Estudo dos polimorfismos de base única (SNPs) na região promotora dos genes das citocinas TGF- 1 e IL-1 associados à malária e à infecção assintomática por Plasmodium spp. na região do rio Negro, Amazonas, Brasil
This project focuses on the study of single base polymorphisms (SNPs) in cytokine genes and their association with susceptibility/resistance to the disease, with the objective of determining whether polymorphisms in the regulatory regions of these genes can cause a dysregulation in the expression of these cytokines, influencing the susceptibility and /or resistance to clinical malaria and asymptomatic plasmodial infection.
The pathogenesis of malaria is complex and the clinical presentation is characterized by a wide spectrum ranging from asymptomatic forms to severe disease, which can even lead to death. However, the factors that cause an individual to be asymptomatic are still unknown. The clinical and epidemiological variability of malaria seems to be associated with genetic factors. Cytokines play an important role both in protection and in the pathogenesis of malaria, so that polymorphisms in their genes have been associated with protection and/or susceptibility to infection. It is proposed to sequence the promoter regions of the TGF-1 and IL-1 cytokine genes in 800 individuals living in the municipality of Barcelos with the purpose of identifying SNPs and haplotypes and their allelic frequencies. Subjects will be divided into the following groups of subjects: 1) with asymptomatic infection, 2) with clinical malaria, 3) uninfected but with a past history of malaria, and 4) who have never had malaria. After the analysis and identification of SNPs and haplotypes, clinical association studies will be carried out, evaluating possible roles of these SNPs as “genetic markers” of susceptibility and/or resistance. The validation of the clinical associations of the SNPs will be done through real-time PCR assays (TaqMan) and measurement of cytokines in the serum in order to determine whether the polymorphisms found in the promoter region of these genes are influencing their expression. These cytokines were chosen based on previous studies that suggested that they are important regulators of the cellular immune response to malaria, and several polymorphisms have already been identified in these genes, and their associations with malaria validated in previous studies in other populations. The promoter regions of the proposed genes have not yet been studied in the upper Rio Negro and the project will allow us to complete our group’s initial research proposal.
Feb 2016
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