Abstract
BackgroundCytokines play an important role in human immune responses to malaria and variation in their production may influence the course of infection and determine the outcome of the disease. The differential production of cytokines has been linked to single nucleotide polymorphisms in gene promoter regions, signal sequences, and gene introns. Although some polymorphisms play significant roles in susceptibility to malaria, gene polymorphism studies in Brazil are scarce.MethodsA population of 267 individuals from Brazilian Amazon exposed to malaria was genotyped for five single nucleotide polymorphisms (SNPs), IFNG + 874 T/A, IL10A-1082G/A, IL10A-592A/C, IL10A-819 T/C and NOS2A-954G/C. Specific DNA fragments were amplified by polymerase chain reaction, allowing the detection of the polymorphism genotypes. The polymorphisms IL10A-592A/C and IL10A-819 T/C were estimated by a single analysis due to the complete linkage disequilibrium between the two SNPs with D’ = 0.99. Plasma was used to measure the levels of IFN-γ and IL-10 cytokines by Luminex and nitrogen radicals by Griess reaction.ResultsNo differences were observed in genotype and allelic frequency of IFNG + 874 T/A and NOS2A-954G/C between positive and negative subjects for malaria infection. Interesting, the genotype NOS2A-954C/C was not identified in the study population. Significant differences were found in IL10A-592A/C and IL10A-819 T/C genotypes distribution, carriers of IL10A -592A/-819 T alleles (genotypes AA/TT + AC/TC) were more frequent among subjects with malaria than in negative subjects that presented a higher frequency of the variant C allele (p < 0.0001). The presence of the allele C was associated with low producer of IL-10 and low parasitaemia. In addition, the GTA haplotypes formed from combinations of investigated polymorphisms in IL10A were significantly associated with malaria (+) and the CCA haplotype with malaria (−) groups. The IL10A-1082G/A polymorphism showed high frequency of heterozygous AG genotype in the population, but it was not possible to infer any association of the polymorphism because their distribution was not in Hardy Weinberg equilibrium.ConclusionThis study shows that the IL10A-592A/C and IL10A-819 T/C polymorphisms were associated with malaria and decreased IL-10 levels and low parasite density suggesting that this polymorphism influence IL-10 levels and may influence in the susceptibility to clinical malaria.
Highlights
Cytokines play an important role in human immune responses to malaria and variation in their production may influence the course of infection and determine the outcome of the disease
Description of the studied population The epidemiological surveillance shows that a significant proportion (93.16%) of the inhabitants reported a prior infection with P. vivax and/or P. falciparum indicating that the majority of the individuals were exposed to malaria parasite throughout the years
In malaria (+) group, 53 (72.6%) individuals were infected with P. vivax and 20 (27.4%) with P. falciparum, consistent with Plasmodium species distribution reported by the Brazilian Ministry of Health [34]
Summary
Cytokines play an important role in human immune responses to malaria and variation in their production may influence the course of infection and determine the outcome of the disease. Some polymorphisms play significant roles in susceptibility to malaria, gene polymorphism studies in Brazil are scarce. Beyond the pathogenic potential of the parasite, there are environmental factors, host genetics and parasite virulence associated to susceptibility and resistance to malaria [1,2]. Several studies have demonstrated that the presence of polymorphisms in IFN-γ, IL-10 and NO gene have been associated with susceptibility or resistance to various diseases [11,12,13,14,15]
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