Polygenic Control of Human T Lymphotropic Virus Type I (HTLV-I) Provirus Load and the Risk of HTLV-I–Associated Myelopathy/Tropical Spastic Paraparesis

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-α allowed for the correct identification of 88% of cases of HAM/TSP in this Japanese cohort