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Evaluation of host genetic and viral factors as surrogate markers for HTLV‐1‐associated myelopathy/tropical spastic paraparesis in Peruvian HTLV‐1‐infected patients
Author(s) -
Talledo Michael,
López Giovanni,
Huyghe Jeroen R.,
Verdonck Kristien,
Adaui Vanessa,
González Elsa,
Best Iván,
Clark Daniel,
Vanham Guido,
Gotuzzo Eduardo,
Van Camp Guy,
Van Laer Lut
Publication year - 2010
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.21675
Subject(s) - tropical spastic paraparesis , virology , myelopathy , host (biology) , surrogate endpoint , biology , immunology , viral load , medicine , human immunodeficiency virus (hiv) , genetics , neuroscience , spinal cord
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 ‐α −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. © 2010 Wiley‐Liss, Inc.

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