Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.
To investigate non-human leukocyte antigen candidate genes that influence the outcome of human T cell lymphotropic virus (HTLV) type I infection, we analyzed 6 single-nucleotide polymorphisms in the interleukin (IL)-10 promoter region in 280 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 255 HTLV-I-seropositive asymptomatic carriers from an area where HTLV-I is endemic. The IL-10 -592 A allele, which shows lower HTLV-I Tax-induced transcriptional activity than the C allele in the Jurkat T cell line, was associated with a >2-fold reduction in the odds of developing HAM/TSP (P=.011; odds ratio [OR], 0.50 [95% confidence interval, 0.30-0.86]) by reducing the provirus load in the whole cohort (P=.009, analysis of variance). Given the OR and the observed frequency of IL-10 -592 A, we demonstrate that this allele prevents approximately 44.7% (standard deviation, +/-13.1%) of potential cases of HAM/TSP, which indicates that it defines one component of the genetic susceptibility to HAM/TSP in the cohort.
Sabouri
Amir H
AH
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Saito
Mineki
M
Lloyd
Alun L
AL
Vine
Alison M
AM
Witkover
Aviva W
AW
Furukawa
Yoshitaka
Y
Izumo
Shuji
S
Arimura
Kimiyoshi
K
Marshall
Sara E F
SE
Usuku
Koichiro
K
Bangham
Charles R M
CR
Osame
Mitsuhiro
M
D000483:Alleles; D016356:Gene Products, tax / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D015493:Paraparesis, Tropical Spastic / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000302:isolation & purification*; D012306:Risk; D019562:Viral Load
D016356:Gene Products, tax; D016753:Interleukin-10