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Background   DDX39B (BAT1)  encodes an RNA helicase known to regulate expression of TNF and IL-6. Elevated levels of these two cytokines are associated with increased severity of clinical malaria. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in the  DDX39B ,  TNF  and  IL6  genes and the clinical outcomes of patients with  Plasmodium vivax  malaria.    Methods  Cross-sectional investigations were carried out in two regions of the Brazilian Amazon where several studies on the pathogenesis of vivax malaria had been performed. Individuals were categorized according to infection status as well as clinical presentation into the following groups: uninfected, asymptomatic infection, mild infection, or complicated infection. Polymorphisms were identified using PCR restriction fragment-length polymorphism analysis and the restriction enzymes  Nl aIII or  Nco I. The plasma levels of cytokines were determined using ELISA.    Results  The G allele of  DDX39B- 22C > G was associated with absent or decreased manifestations of malaria and the C allele was a risk factor for disease complications. Study participants heterozygous for  TNF-308  (GA) and  DDX39B-348  (CT) had higher TNF levels than wild-type participants. Haplotypes that included  DDX39B  (-22C > G and -348C > T) and  TNF  polymorphisms were not directly associated with mild or complicated malaria infections; however, haplotypes AGC, ACC, GGT, AGT and ACT were associated with increased TNF levels. Participants with genotype combinations GC/CC/GG/GG and GG/CT/GG/GG ( DDX39B-22 / DDX39B-348 / TNF-308 / IL6-176 ) had decreased and increased risk of mild malaria, respectively, compared with asymptomatic and uninfected participants. GC/CC/GG/GG was linked to decreased TNF and IL-6 levels.    Conclusions  This is the first study to describe patients with  DDX39B  and  IL6  SNPs who had vivax malaria. These findings support the postulation that a set of mutations in immune-related genes is associated with inflammatory mediators and the clinical outcomes of patients with malaria.

DDX39B (BAT1), TNF and IL6 gene polymorphisms and association with clinical outcomes of patients with Plasmodium vivax malaria