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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,3,16]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Human T cell leukemia virus type 1 (HTLV-1) proviral load is associated with the risk of developing HTLV-1\u2013associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) and several small-scale candidate gene approaches have also identified associations of particular\n                    <jats:italic>HLA<\/jats:italic>\n                    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\n                    <jats:italic>HLA<\/jats:italic>\n                    genes, we found that\n                    <jats:italic>HLA-DRB1<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2004199118","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T16:26:19Z","timestamp":1614615979000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["Genome wide association study of HTLV-1\u2013associated myelopathy\/tropical spastic paraparesis in the Japanese population"],"prefix":"10.1073","volume":"118","author":[{"given":"Marina","family":"Penova","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8507 Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4045-6518","authenticated-orcid":false,"given":"Shuji","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, 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Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, 216-8511 Kanagawa, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8344-5472","authenticated-orcid":false,"given":"Meiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8507 Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8507 Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8208-5586","authenticated-orcid":false,"given":"Mineki","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kawasaki Medical School, Kurashiki, 701-0192 Okayama, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7219-5589","authenticated-orcid":false,"given":"Kunihiro","family":"Tsukasaki","sequence":"additional","affiliation":[{"name":"Department of Hematology, International Medical Center, Saitama Medical University, Hidaka, 350-1298 Saitama, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kamigyo-ku, 602-8566 Kyoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-8468","authenticated-orcid":false,"given":"Norihiro","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kansai Medical University, Hirakata, 573-1010 Osaka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3289-3555","authenticated-orcid":false,"given":"Hideo","family":"Hara","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, 849-8501 Saga, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-8853","authenticated-orcid":false,"given":"Eiji","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544 Kagoshima, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Nozuma","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544 Kagoshima, 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Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Uchimaru","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato-ku, 108-8639 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-6192","authenticated-orcid":false,"given":"Masako","family":"Iwanaga","sequence":"additional","affiliation":[{"name":"Department of Frontier Life Sciences, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588 Nagasaki, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-406X","authenticated-orcid":false,"given":"Atae","family":"Utsunomiya","sequence":"additional","affiliation":[{"name":"Department of Hematology, Imamura General Hospital, Kagoshima, 890-0064 Kagoshima, 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Rafatpanah ., Association between HLA-DRB1*01 and HLA-Cw*08 and outcome following HTLV-I infection. Iran. J. Immunol. 4, 94\u2013100 (2007).","journal-title":"Iran. J. 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