Dataset Information

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

ABSTRACT:

Background

The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP.

Methods

The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System.

Results

A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95%?= 0.96-4.27) and in rs8099917 genotype GG (OR = 7.61; IC95%? = 1.82-31.72).

Conclusion

Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.

SUBMITTER: Assone T

PROVIDER: S-EPMC4169378 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

Assone Tatiane T de Souza Fernando Vieira FV Gaester Karen Oliveira KO Fonseca Luiz Augusto Marcondes LA Luiz Olinda do Carmo Odo C Malta Fernanda F Pinho João Renato Rebello JR Gonçalves Fernanda de Toledo Fde T Duarte Alberto Jose da Silva AJ de Oliveira Augusto Cesar Penalva AC Casseb Jorge J

PLoS neglected tropical diseases 20140918 9

<h4>Background</h4>The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP.<h4>Methods</h4>The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantifie ...[more]

PMID: 25233462

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Project description:Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as a surrogate CSF biomarker to identify HAM/TSP patients with a worse prognosis.

Dataset Information

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

Background

Methods

Results

Conclusion

Publications

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

Similar Datasets

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