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-15 191 C 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