title: 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.
abstract: 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.
authors.affiliation: Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Sabouri
authors.forename: Mineki
authors.initials: M
authors.lastname: Saito
authors.forename: Alun L
authors.initials: AL
authors.lastname: Lloyd
authors.forename: Alison M
authors.initials: AM
authors.lastname: Vine
authors.forename: Aviva W
authors.initials: AW
authors.lastname: Witkover
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Izumo
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Arimura
authors.forename: Sara E F
authors.initials: SE
authors.lastname: Marshall
authors.forename: Koichiro
authors.initials: K
authors.lastname: Usuku
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Osame
mesh_terms: 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
chemical_list: D016356:Gene Products, tax; D016753:Interleukin-10