2002•The Journal of Infectious DiseasesRequires access
Polygenic Control of Human T Lymphotropic Virus Type I (HTLV‐I) Provirus Load and the Risk of HTLV‐I–Associated Myelopathy/Tropical Spastic Paraparesis
Alison M. Vine, Aviva Witkover, Alun L. Lloyd, Katie Jeffery, Asna A. Siddiqui, Sara E. Marshall, Mike Bunce, Nobutaka Eiraku, Shuji Izumo, Koichiro Usuku, Mitsuhiro Osame, Charles R. M. Bangham
Open publisher page 93 citations
Abstract
Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one outcome of infection with HTLV-I. A population association study of 229 patients with HAM/TSP and 202 healthy carriers of HTLV-I in southern Japan showed that this outcome of HTLV-I infection and the HTLV-I provirus load are under polygenic control. Of 58 polymorphic sites studied in 39 non-HLA candidate gene loci, 3 new host genetic factors that influenced the risk of HAM/TSP or the provirus load of HTLV-I were identified. The promoter TNF -863A allele predisposed to HAM/TSP, whereas SDF-1 +801A 3'UTR, and IL-15 191C alleles conferred protection. Knowledge of HTLV-I-infected individuals' ages, sex, provirus load, HTLV-I subgroup, and genotypes at the loci HLA-A, HLA-C, SDF-1, and TNF-alpha allowed for the correct identification of 88% of cases of HAM/TSP in this Japanese cohort.