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These severe cutaneous drug reactions are known to be caused by inciting drugs and infectious agents. Previously, we have reported the association of\u00a0\n                    <jats:italic>HLA-A*02:06<\/jats:italic>\n                    \u00a0and\u00a0\n                    <jats:italic>HLA-B*44:03<\/jats:italic>\n                    \u00a0with cold medicine (CM)-related SJS\/TEN with severe ocular complications (SOCs) in the Japanese population. However, the conventional HLA typing method (PCR-SSOP) sometimes has ambiguity in the final HLA allele determination. In this study, we performed HLA-disease association studies in CM-SJS\/TEN with SOCs at 3- or 4-field level. 120 CM-SJS\/TEN patients with SOCs and 817 Japanese healthy controls are HLA genotyped using the high-resolution next-generation sequencing (NGS)-based HLA typing of HLA class I genes, including\u00a0\n                    <jats:italic>HLA-A<\/jats:italic>\n                    ,\u00a0\n                    <jats:italic>HLA-B<\/jats:italic>\n                    , and\u00a0\n                    <jats:italic>HLA-C<\/jats:italic>\n                    . Among the alleles of HLA class I genes,\u00a0\n                    <jats:italic>HLA-A*02:06:01<\/jats:italic>\n                    \u00a0was strongly associated with susceptibility to CM-SJS\/TEN (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.15\u2009\u00d7\u200910\n                    <jats:sup>\u221218<\/jats:sup>\n                    , odds ratio\u2009=\u20095.46). Four other alleles (\n                    <jats:italic>HLA-A*24:02:01<\/jats:italic>\n                    ,\u00a0\n                    <jats:italic>HLA-B*52:01:01<\/jats:italic>\n                    ,\u00a0\n                    <jats:italic>HLA-B*46:01:01<\/jats:italic>\n                    , and\u00a0\n                    <jats:italic>HLA-C*12:02:02<\/jats:italic>\n                    )\u00a0also demonstrated significant associations. HLA haplotype analyses indicated that\u00a0\n                    <jats:italic>HLA-A*02:06:01<\/jats:italic>\n                    \u00a0is primarily associated with susceptibility to CM-SJS\/TEN with SOCs. Notably, there were no specific disease-causing rare variants among the high-risk HLA alleles. This study highlights the importance of higher resolution HLA typing in the study of disease susceptibility, which may help to elucidate the pathogenesis of CM-SJS\/TEN with SOCs.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-52619-2","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T06:05:02Z","timestamp":1573106702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Identification of HLA-A*02:06:01 as the primary disease susceptibility HLA allele in cold medicine-related Stevens-Johnson syndrome with severe ocular complications by high-resolution NGS-based HLA typing"],"prefix":"10.1038","volume":"9","author":[{"given":"Ken","family":"Nakatani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Ueta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-4731","authenticated-orcid":false,"given":"Seik-Soon","family":"Khor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-7875","authenticated-orcid":false,"given":"Yuki","family":"Hitomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Okudaira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anri","family":"Masuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Sotozono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Inoko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsushi","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"52619_CR1","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1056\/NEJM199512143332404","volume":"333","author":"JC Roujeau","year":"1995","unstructured":"Roujeau, J. 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