Lack of association between single-nucleotide polymorphisms of pro- and anti-inflammatory cytokines and HTLV-1-associated myelopathy / tropical spastic paraparesis development in patients from Rio de Janeiro, Brazil

Abstract

BackgroundHTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce.MethodsThe genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated.ResultsLack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers.ConclusionsWe did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms.

Pathogenesis of HTLV-1 infection and progression biomarkers: An overview

“…Recently, one study reported an association between polymorphisms in the TREX and SAMHD1 genes and increased proviral load of HTLV-1 among people with HAM [ 92 , 93 ]; similar results had also been described previously [ 88 , 94 , 95 , 96 ]. These data reinforce the need for further epidemiological genetic studies involving a larger number of people infected with HTLV-1 to better understand the effect of these markers on the pathogenesis and natural history of HAM.…”

Influence of Immunogenetic Biomarkers in the Clinical Outcome of HTLV-1 Infected Persons

“…In contrast, Schor et al [56], in a case-control study, reported the absence of association between single nucleotide polymorphisms of pro- and anti-inflammatory cytokines ( TNFA −308G/A, IL6 −174G/C, IFNG +874T/A, TGFB ) and HAM patients from Brazil.…”

“…The wild-type allele of the IL10 −592A/C polymorphism was associated with HTLV-1 transcriptional activity mediated by the Tax protein, influencing both HTLV-1 proviral load and a 2-fold reduction on the chances of developing HAM [59]. According to Schor et al [56] the IL10 −592AA genotype is associated with higher proviral load. However, the investigation of this polymorphism, together with others located in the IL10 gene, showed that IL10 −819*C/T and −592*C/A polymorphisms may contribute to susceptibility to infection by HTLV-1, although it does not appear to be related to the protection against HAM development [61].…”