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

Jason Rosado, Sandra Morales, Giovanni López, Daniel Clark, Kristien Verdonck, Eduardo Gotuzzo, Guy Van Camp, Michael Talledo

Research output: Contribution to journalA1: Web of Science-article

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.

Original languageEnglish
JournalJournal of Medical Virology
Volume89
Issue number4
Pages (from-to)726-731
Number of pages6
ISSN0146-6615
DOIs
Publication statusPublished - 2017

Keywords

  • Cohort Studies
  • Female
  • Genotype
  • HTLV-I Infections
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Proviruses
  • Viral Load
  • fas Receptor
  • Journal Article

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