Evaluation of host genetic and viral factors as surrogate markers for HTLV-1-associated myelopathy/tropical spastic paraparesis in Peruvian HTLV-1-infected patients

J Med Virol. 2010 Mar;82(3):460-6. doi: 10.1002/jmv.21675.

Abstract

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a complication that affects up to 5% of HTLV-1-infected individuals. Several host genetic and viral factors have been associated with the risk of HAM/TSP. The aim of this study was to evaluate the performance of a prognostic model for HAM/TSP developed in Japan in a Peruvian population of 71 HAM/TSP patients and 94 asymptomatic carriers (ACs). This model included age, proviral load (PVL), the presence of HLA-A*02 and HLA-Cw*08 alleles, SDF-1 +801, and TNF-alpha -863 polymorphisms, and viral subgroup. We describe frequencies for the four host genetic markers and demonstrate the presence of the HTLV-1 tax B subgroup in Peru. Using cross-validation, we show that the predictive ability of the prognostic model, as characterized by the area under the receiver-operating characteristic curve (AUC), does not differ from a model containing PVL only (both AUC = 0.74). We found some suggestive evidence of a protective effect of the HLA-A*02 allele but failed to replicate the associations with the other three genetic markers and with viral subgroup. A logistic model containing PVL, age, gender, and HLA-A*02 provided the best predictive ability in the Peruvian cohort (AUC = 0.79). J. Med. Virol. 82:460-466, 2010. (c) 2010 Wiley-Liss, Inc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Biomarkers
  • Female
  • HLA Antigens / genetics*
  • HTLV-I Infections / complications*
  • HTLV-I Infections / genetics
  • HTLV-I Infections / virology
  • Human T-lymphotropic virus 1 / isolation & purification*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Paraparesis, Tropical Spastic / diagnosis*
  • Peru
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Prognosis
  • Proviruses / isolation & purification
  • Risk Factors
  • Tumor Necrosis Factor-alpha / genetics*
  • Viral Load
  • Young Adult

Substances

  • Biomarkers
  • HLA Antigens
  • Tumor Necrosis Factor-alpha