Both Provirus Load and the Risk of Human T Lymphotropic Virus Type I–Associated

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 12-fold reduction in the odds of developing HAM/TSP ( ; odds ratioPp.011 [OR], 0.50 [95 % confidence interval, 0.30–0.86]) by reducing the provirus load in the whole cohort (Pp, analysis of variance). Given the OR and the observed frequency of IL-10 592 A, we demonstrate that.009 this allele prevents ∼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. Human T-cell lymphotropic virus (HTLV) type I is the first characterized human retrovirus [1, 2] and is as-sociated with adult T cell leukemia (ATL) [3, 4] and HTLV-I–associated myelopathy/tropical spastic para-paresis (HAM/TSP) [5, 6]. Unlike HIV, HTLV-I cause