Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population
Marina Penova, Shuji Kawaguchi, Jun‐ichirou Yasunaga, Takahisa Kawaguchi, Tomoo Sato, Meiko Takahashi, Masakazu Shimizu, Mineki Saito, Kunihiro Tsukasaki, Masanori Nakagawa, Norihiro Takenouchi, Hideo Hara, Eiji Matsuura, Satoshi Nozuma, Hiroshi Takashima, Shuji Izumo, Toshiki Watanabe, Kaoru Uchimaru, Masako Iwanaga, Atae Utsunomiya, Yasuharu Tabara, Richard Paúl, Yoshihisa Yamano, Masao Matsuoka, Fumihiko Matsuda
Abstract
Significance Human T cell leukemia virus type 1 (HTLV-1) proviral load is associated with the risk of developing HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several small-scale candidate gene approaches have also identified associations of particular HLA alleles with HAM/TSP risk. However, no large-scale genome-wide association (GWA) studies have been performed to date. By a large-scale GWA study and comprehensive genotyping of classical HLA genes, we found that HLA-DRB1 alleles carrying leucine at the antigen presentation groove domain (DRB1-GB-7-Leu) increased the susceptibility to HAM/TSP. Individuals who were homozygous for DRB1-GB-7-Leu had a ninefold increased odds of developing HAM/TSP. This effect of DRB1-GB-7-Leu was independent of proviral load. These findings identify DRB1-GB-7-Leu as a genetic risk marker of HAM/TSP development.