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The FAS‐670 AA genotype is associated with high proviral load in peruvian HAM/TSP patients
Author(s) -
Rosado Jason,
Morales Sandra,
López Giovanni,
Clark Daniel,
Verdonck Kristien,
Gotuzzo Eduardo,
Van Camp Guy,
Talledo Michael
Publication year - 2017
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.24681
Subject(s) - virology , genotype , biology , genetics , gene
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.