The FAS-670 AA genotype is associated with high proviral load in peruvian HAM/TSP patients.
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.
Molecular Epidemiology Laboratory, Institute of Tropical Medicine Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Jason
J
Rosado
Molecular Epidemiology Laboratory, Institute of Tropical Medicine Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Sandra
S
Morales
Molecular Epidemiology Laboratory, Institute of Tropical Medicine Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Giovanni
G
López
Laboratories of Research and Development, Faculty of Science, Universidad Peruana Cayetano Heredia, Lima, Peru.
Daniel
D
Clark
Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium.
Kristien
K
Verdonck
Faculty of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru.|Institute of Tropical Medicine Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Eduardo
E
Gotuzzo
Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Guy
G
Van Camp
Molecular Epidemiology Laboratory, Institute of Tropical Medicine Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.|Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Michael
M
Talledo
D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015490:HTLV-I Infections / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011533:Proviruses / Q000235:genetics*; D019562:Viral Load; D019014:fas Receptor / Q000235:genetics*
C491901:FAS protein, human; D019014:fas Receptor
HTLV-I-associated myelopathy-tropical spastic paraparesis; Human T-lymphotropic virus 1; antigens, CD95; polymorphism, single nucleotide; proviral load