Evaluation of host genetic and viral factors as surrogate markers for HTLV-1-associated myelopathy/tropical spastic paraparesis in Peruvian HTLV-1-infected patients.
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.
Talledo
Michael
M
Institute of Tropical Medicine Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. 11936@upch.edu.pe
López
Giovanni
G
Huyghe
Jeroen R
JR
Verdonck
Kristien
K
Adaui
Vanessa
V
González
Elsa
E
Best
Iván
I
Clark
Daniel
D
Vanham
Guido
G
Gotuzzo
Eduardo
E
Van Camp
Guy
G
Van Laer
Lut
L
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D015490:HTLV-I Infections / Q000150:complications* / Q000235:genetics / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000175:diagnosis*; D010568:Peru; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D011533:Proviruses / Q000302:isolation & purification; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D019562:Viral Load; D055815:Young Adult
D015415:Biomarkers; D006680:HLA Antigens; D014409:Tumor Necrosis Factor-alpha