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

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 DDX39...

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Bibliographic Details
Published in:Malaria journal 2014-07, Vol.13 (1), p.278-278, Article 278
Main Authors: Mendonça, Vitor R R, Souza, Ligia C L, Garcia, Gabriela C, Magalhães, Belisa M L, Lacerda, Marcus V G, Andrade, Bruno B, Gonçalves, Marilda S, Barral-Netto, Manoel
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Alleles
Anemia - etiology
Brazil
Chemokines
Child
Child, Preschool
Chromosomes, Human, Pair 6 - genetics
Chronic illnesses
Clinical outcomes
Confidence intervals
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - physiology
Deoxyribonucleic acid
Disease Resistance - genetics
DNA
Drug therapy
Experiments
Female
Field study
Genetic aspects
Genetic Predisposition to Disease - genetics
Genotype
Haplotypes - genetics
HIV
Human immunodeficiency virus
Humans
Hyperbilirubinemia - etiology
Infant
Infections
Interleukin-6 - blood
Interleukin-6 - genetics
Malaria
Malaria, Vivax - complications
Malaria, Vivax - genetics
Malaria, Vivax - immunology
Male
Medical research
Medicine, Experimental
Middle Aged
Mutation
Parasitic diseases
Plasma
Plasmodium vivax
Polymerase chain reaction
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Polypeptides
Proteins
Respiratory Insufficiency - etiology
Risk
Seizures - etiology
Single nucleotide polymorphisms
Treatment Outcome
Tropical diseases
Tumor Necrosis Factor-alpha - blood
Tumor Necrosis Factor-alpha - genetics
Young Adult
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Summary: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. 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 NlaIII or NcoI. The plasma levels of cytokines were determined using ELISA. 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. 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.
ISSN:1475-2875
1475-2875
DOI:10.1186/1475-2875-13-278