Abstract
BackgroundMalaria is among the most prevalent parasitic diseases worldwide. In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. The role of genetic factors in host immune system conferring resistance/susceptibility against P. vivax infections is still poorly understood.MethodsThe present study investigates the influence of polymorphisms in 18 genes related to the immune system in patients with malaria caused by P. vivax. A total of 263 healthy individuals (control group) and 216 individuals infected by P. vivax (malaria group) were genotyped for 33 single nucleotide polymorphisms (SNPs) in IL1B, IL2, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, IL12RB1, SP110, TNF, TNFRSF1A, IFNG, IFNGR1, VDR, PTPN22 and P2X7 genes. All subjects were genotyped with 48 ancestry informative insertion-deletion polymorphisms to determine the proportion of African, European and Amerindian ancestry. Only 13 SNPs in 10 genes with differences lower than 20% between cases and controls in a Poisson Regression model with age as covariate were further investigated with a structured population association test.ResultsThe IL1B gene -5839C > T and IL4R 1902A > G polymorphisms and IL12RB1 -1094A/-641C and TNF -1031 T/-863A/-857 T/-308 G/-238 G haplotypes were associated with malaria susceptibility after population structure correction (p = 0.04, p = 0.02, p = 0.01 and p = 0.01, respectively).ConclusionPlasmodium vivax malaria pathophysiology is still poorly understood. The present findings reinforce and increase our understanding about the role of the immune system in malaria susceptibility.
Highlights
Malaria is among the most prevalent parasitic diseases worldwide
The 33 single nucleotide polymorphisms (SNP) investigated, their location in the gene and the allele frequencies observed in malaria cases and controls are shown in Additional file 1
In a gene-based association study with 18 candidate genes for malaria susceptibility using 33 SNPs as genetic markers, this study demonstrated that IL1B, IL4R, IL12RB1 and tumour necrosis factor (TNF) genes were associated with susceptibility to P. vivax malaria in a population of Pará state, Brazil
Summary
In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. Malaria remains one of the most important parasitic infections in the world with almost 250 million new cases diagnosed annually [1]. It is caused by infection with one or more of five species of Plasmodium parasites. The most obvious features that distinguish P. vivax from P. falciparum include the development of dormant forms (hypnozoites) in the liver that cause subsequent infections in the blood called relapses, which add a substantial number of cases to the general burden of the disease and present one of the most challenging bottlenecks for vivax malaria eradication [7]
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