The FAS‐670 AA genotype is associated with high proviral load in peruvian HAM/TSP patients

Abstract

Human T-lymphotropic virus 1 (HTLV-1) is the etiologic agent of the HTLV-1-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. As 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. 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). 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. J. Med. Virol. 89:726-731, 2017. © 2016 Wiley Periodicals, Inc.

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

“…Recently, FAS −670 AA genotype was associated with high proviral load as compared to FAS −670 GG in HAM patients [70]. This result is in agreement with our study, where the genotype FAS −670AA was more frequent among HAM patients as compared to the asymptomatic individuals [69], suggesting that individuals carrying this genotype have a greater chance and a higher susceptibility to progress to overt clinical disease.…”

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.…”

Family Aggregation of HTLV-1 Infection Associated with FAS -670A/G Polymorphism: A Case Report

“…Among HAM/TSP patients, FAS levels correlated positively with lymphocyte activation, but the increased lymphocyte FAS expression was linked to decreased apoptosis and increased lymphoproliferation in cell culture and a strong increase in cellular FAS expression upon HAM/TSP progression ( Menezes et al, 2017 ). Moreover, Rosado et al (2017) found an association between the FAS -670 AA genotype and the higher proviral load among HAM/TSP patients.…”

“…The search for host immunogenetic markers, possibly associated with HTLV-1 infection and progression to disease was pursued by our research group in the Amazon region of Brazil and other groups elsewhere ( Nishimura et al, 1991 ; Jeffery et al, 2000 ; Pontes et al, 2005 ; Alves et al, 2007 ; Vallinoto et al, 2012 , 2015 ; de Sá et al, 2016 ; Rosado et al, 2017 ). Polymorphisms rs1800450 (allele B, codon 54) and rs1800682 (-670A/G) located in MBL2 and FAS genes, respectively, were strongly associated with HTLV-1 infection.…”