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

• Published in: The Journal of infectious diseases 2004-10, Vol.190 (7), p.1279-1285
• Main Authors: Sabouri, Amir H., Saito, Mineki, Lloyd, Alun L., Vine, Alison M., Witkover, Aviva W., Furukawa, Yoshitaka, Izumo, Shuji, Arimura, Kimiyoshi, Marshall, Sara E. F., Usuku, Koichiro, Bangham, Charles R. M., Osame, Mitsuhiro
• Format: Article
• Language: English
• Subjects: Alleles; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Products, tax - physiology; Genotypes; Human T lymphotropic virus 1; Human T-lymphotropic virus; Human T-lymphotropic virus 1 - genetics; Infectious diseases; Interleukin-10 - genetics; Medical genetics; Medical sciences; Microbiology; Miscellaneous; Nervous system diseases; Paraparesis, Tropical Spastic - etiology; Paraparesis, Tropical Spastic - genetics; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Proviruses; Proviruses - isolation & purification; Risk; Spastic paraparesis; T cell leukemia; T lymphocytes; Viral Load; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/423942

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 ∼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.