{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:21:49Z","timestamp":1780647709688,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T00:00:00Z","timestamp":1506556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine, which is used to treat inflammatory joint and bowel disease. We performed a genome\u2010wide association study comprising 9,380,034 polymorphisms and 180 HLA alleles in 36 cases of sulfasalazine\u2010induced agranulocytosis and 5,170 population controls. Sulfasalazine\u2010induced agranulocytosis was significantly associated with the HLA region on chromosome 6. The top hit (rs9266634) was located close to<jats:italic>HLA\u2010B<\/jats:italic>, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69)<jats:italic>P<\/jats:italic>\u2009=\u20092.55 \u00d7 10<jats:sup>\u22128<\/jats:sup>). We HLA\u2010sequenced a second cohort consisting of 40 cases and 142 treated controls, and confirmed significant associations with<jats:italic>HLA\u2010B*08:01<\/jats:italic>, OR\u2009=\u20092.25 (95% CI (1.02, 4.97)<jats:italic>P<\/jats:italic>\u2009=\u20090.0439), in particular the<jats:italic>HLA\u2010B*08:01<\/jats:italic>haplotype<jats:italic>HLA\u2010DQB1*02:01\u2010DRB1*03:01\u2010B*08:01\u2010C*07:01<\/jats:italic>, OR\u2009=\u20093.79 (95% CI (1.63, 8.80)<jats:italic>P<\/jats:italic>\u2009=\u20090.0019), and with<jats:italic>HLA\u2010A*31:01<\/jats:italic>, OR\u2009=\u20094.81 (95% CI (1.52, 15.26)<jats:italic>P<\/jats:italic>\u2009=\u20090.0077). The number needed to test for<jats:italic>HLA\u2010B*08:01<\/jats:italic>and<jats:italic>HLA\u2010A*31:01<\/jats:italic>to avoid one case was estimated to be 1,500. We suggest that intensified monitoring or alternative treatment should be considered for known carriers of<jats:italic>HLA\u2010B*08:01<\/jats:italic>or<jats:italic>HLA\u2010A*31:01<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/cpt.805","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T09:44:54Z","timestamp":1501580694000},"page":"843-853","source":"Crossref","is-referenced-by-count":19,"title":["Sulfasalazine\u2010Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus"],"prefix":"10.1111","volume":"103","author":[{"given":"Mia","family":"Wadelius","sequence":"first","affiliation":[{"name":"Department of Medical Sciences Clinical Pharmacology and Science for Life Laboratory, Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niclas","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Uppsala Clinical Research Center and Department of Medical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold","family":"Kreutz","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Institut f\u00fcr Klinische Pharmakologie und Toxikologie Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Bondon\u2010Guitton","sequence":"additional","affiliation":[{"name":"Service de Pharmacologie M\u00e9dicale et Clinique Centre Hospitalier Universitaire, Facult\u00e9 de M\u00e9decine de l'Universit\u00e9 de Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Iba\u00f1ez","sequence":"additional","affiliation":[{"name":"Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona, Fundaci\u00f3 Institut Catal\u00e0 de Farmacologia Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Carvajal","sequence":"additional","affiliation":[{"name":"Centro de Estudios sobre la Seguridad de los Medicamentos Universidad de Valladolid Valladolid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Isabel","family":"Lucena","sequence":"additional","affiliation":[{"name":"S Farmacologia Clinica Instituto de Investigaci\u00f3n Biomedica de M\u00e1laga (IBIMA), H Universitario Virgen de la Victoria, Universidad de M\u00e1laga, CIBERehd Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Sancho Ponce","sequence":"additional","affiliation":[{"name":"Servei d'Hematologia i Banc de Sang Hospital General de Catalunya Sant Cugat del Vall\u00e8s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Molokhia","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London Department of Primary Care and Public Health Sciences London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Martin","sequence":"additional","affiliation":[{"name":"Instituto de Parasitologia y Biomedicina Lopez\u2010Neyra, CSIC Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Axelsson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Molecular Medicine and Science for Life Laboratory, Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Kohnke","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Clinical Pharmacology and Science for Life Laboratory, Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun\u2010Ying","family":"Yue","sequence":"additional","affiliation":[{"name":"Medical Products Agency Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik K.E.","family":"Magnusson","sequence":"additional","affiliation":[{"name":"Swedish Twin Registry Department of Medical Epidemiology and Biostatistics, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"Department of Immunology Genetics and Pathology, Clinical Immunology, Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4r","family":"Hallberg","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Clinical Pharmacology and Science for Life Laboratory, Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of EuDAC","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,28]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e3282f15fb9"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-013-1618-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-9-200705010-00009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.985649"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.6.3.323"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21433"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198600321-00009"},{"key":"e_1_2_9_8_1","first-page":"577","article-title":"Salazopyrin, a new sulfanilamide preparation","author":"Svartz N.","year":"1942","journal-title":"Acta Med. 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