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

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.