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.