Role of killer cell immunoglobulin-like receptor gene content and human leukocyte antigen-C group in susceptibility to human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis in Peru.
Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) affects approximately 5% of HTLV-1-infected individuals. It is poorly understood why only some infected subjects develop this disease, but host genetic factors may determine susceptibility. The innate immune system may influence disease outcome in HTLV-1-infected individuals because of its role in early immune responses to viral infections. Variation in genes encoding killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) molecule ligands may affect the risk of HAM/TSP. We performed a two-stage case-control study to examine the distribution of KIR genes and HLA-Cw groups in Peruvian HTLV-1-infected HAM/TSP individuals and asymptomatic carriers. We also tested for epistatic effects between specific KIR genes and HLA-Cw groups. In the first stage, we found several trends toward association with HAM/TSP or proviral load (PVL). However, these results were not replicated in the second stage. In conclusion, this is the first report on KIR gene frequencies in the Peruvian population and may be of significance in hematopoietic stem-cell transplants. Our study did not reveal significant associations between KIR genes and HLA-Cw groups and HAM/TSP or PVL. However, because our study was powered to detect only larger effects, additional studies using larger cohorts are needed.
Talledo
Michael
M
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. michaeltalledo@yahoo.com
López
Giovanni
G
Huyghe
Jeroen R
JR
Verdonck
Kristien
K
González
Elsa
E
Clark
Daniel
D
Senitzer
David
D
Vanham
Guido
G
Gotuzzo
Eduardo
E
Van Camp
Guy
G
Van Laer
Lut
L
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015493:Paraparesis, Tropical Spastic / Q000235:genetics* / Q000821:virology; D010568:Peru; D054344:Receptors, KIR2DL3 / Q000235:genetics*
D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D054344:Receptors, KIR2DL3