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The FAS-670 AA genotype is associated with high proviral load in Peruvian HAM/TSP patients.

The FAS-670 AA genotype is associated with high proviral load in Peruvian HAM/TSP patients.
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Rosado J, Morales S, Lopez G, Clark D, Verdonck K, Gotuzzo E, Van Camp G, Talledo M,


Rosado J, Morales S, Lopez G, Clark D, Verdonck K, Gotuzzo E, Van Camp G, Talledo M, (click to view)

Rosado J, Morales S, Lopez G, Clark D, Verdonck K, Gotuzzo E, Van Camp G, Talledo M,

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Journal of medical virology 2016 9 7() doi 10.1002/jmv.24681

Abstract
BACKGROUND
Human T-lymphotropic virus 1 (HTLV-1) is the etiologic agent of the HTLV-I-Associated Myelopathy-Tropical Spastic Paraparesis (HAM/TSP). Apoptosis is a mechanism of defense elicited by many triggers, including cross-linking of the FAS receptor expressed in viruses-infected cells, and the ligand FASL presented by T-cytotoxic cells. Since HAM/TSP has been associated with high levels of proviral load (PVL), we hypothesized that certain genotypes of single-nucleotide polymorphisms (SNPs) associated with a decreased protein expression of FAS and FASL could be risk factors for this disease. Three SNPs: FAS-670A/G (rs1800682), FAS-1377G/A (rs2234767) and FASL-844C/T (rs763110), were analyzed in 73 HAM/TSP patients and 143 HTLV-1 asymptomatic carriers. Ancestry informative markers were used to adjust for ethnicity through a principal component analysis. Gender, age, PVL and the first three principal components were used as covariates.

RESULTS
The FAS/FASL genotype distribution was not associated with HAM/TSP presence (p > 0.05). The FAS-670 AA genotype was associated with high PVL in comparison to FAS-670 GG in HAM/TSP patients (p = 0.015), while in asymptomatic carriers low levels of PVL were observed (p > 0.05).

CONCLUSIONS
Our findings suggest that rs1800682, rs2234767, and rs763110 genotypes are not associated with the presence of HAM/TSP, but that the FAS-670 AA genotype can promote higher PVL values in HAM/TSP patients. This article is protected by copyright. All rights reserved.

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