{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:21:08Z","timestamp":1778538068003,"version":"3.51.4"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2006,10,17]],"date-time":"2006-10-17T00:00:00Z","timestamp":1161043200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2006,10,17]],"date-time":"2006-10-17T00:00:00Z","timestamp":1161043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacogenomics J"],"published-print":{"date-parts":[[2007,10,1]]},"DOI":"10.1038\/sj.tpj.6500423","type":"journal-article","created":{"date-parts":[[2006,9,26]],"date-time":"2006-09-26T12:23:48Z","timestamp":1159273428000},"page":"325-332","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens"],"prefix":"10.1038","volume":"7","author":[{"given":"M","family":"Dettling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Cascorbi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Opgen-Rhein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Schaub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2006,10,17]]},"reference":[{"key":"BF6500423_CR1","first-page":"257","volume":"33","author":"C B\u00e9nichou","year":"1993","unstructured":"B\u00e9nichou C, Solal-Celigny P . Standardization of definitions and criteria for causality assessment of adverse drug reactions. Drug-induced blood cytopenias: report of an international consensus meeting. Nouv Rev Fr Hematol 1993; 33: 257\u2013262.","journal-title":"Nouv Rev Fr Hematol"},{"key":"BF6500423_CR2","doi-asserted-by":"publisher","first-page":"52","DOI":"10.2165\/00003495-198631010-00004","volume":"31","author":"PC Vincent","year":"1986","unstructured":"Vincent PC . Drug-induced aplastic anaemia and agranulocytosis. Drugs 1986; 31: 52\u201363.","journal-title":"Drugs"},{"key":"BF6500423_CR3","first-page":"726","volume":"8","author":"ZC Liu","year":"2000","unstructured":"Liu ZC, Uetrecht JP . Metabolism of ticlopidine by activated neutrophils: implications for ticlopidine-induced agranulocytosis. Drug Metab Dispos 2000; 8: 726\u2013730.","journal-title":"Drug Metab Dispos"},{"key":"BF6500423_CR4","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1021\/tx050095o","volume":"18","author":"I Gardner","year":"2005","unstructured":"Gardner I, Popovic M, Zahid N, Uetrecht JP . A comparison of the covalent binding of clozapine, procainamide, and vesnarinone to human neutrophils in vitro and rat tissues in vitro and in vivo. Chem Res Toxicol 2005; 18: 1384\u20131394.","journal-title":"Chem Res Toxicol"},{"key":"BF6500423_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.schres.2004.05.015","volume":"73","author":"J Hennen","year":"2005","unstructured":"Hennen J, Baldessarini RJ . Suicidal risk during treatment with clozapine: a meta-analysis. Schizophr Res 2005; 73: 139\u2013145.","journal-title":"Schizophr Res"},{"key":"BF6500423_CR6","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJM199307153290303","volume":"329","author":"JM Alvir","year":"1993","unstructured":"Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA . Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med 1993; 329: 162\u2013167.","journal-title":"N Engl J Med"},{"key":"BF6500423_CR7","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1001\/archinte.165.8.869","volume":"25","author":"L Ibanez","year":"2005","unstructured":"Ibanez L, Vidal X, Ballarin E, Laporte JR . Population-based drug-induced agranulocytosis. Arch Intern Med 2005; 25: 869\u2013874.","journal-title":"Arch Intern Med"},{"key":"BF6500423_CR8","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/S0033-3182(99)71206-5","volume":"40","author":"O Oyesanmi","year":"1999","unstructured":"Oyesanmi O, Kunkel EJS, Monti D, Field HL . Hematologic side effects of psychotropics. Psychosomatics 1999; 40: 414\u2013421.","journal-title":"Psychosomatics"},{"key":"BF6500423_CR9","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1046\/j.1365-2796.2001.00915.x","volume":"250","author":"J Palmblad","year":"2001","unstructured":"Palmblad J, Papadaki HA, Eliopoulos D . Acute and chronic neutropenias. What is new? J Intern Med 2001; 250: 476\u2013491.","journal-title":"J Intern Med"},{"key":"BF6500423_CR10","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1054\/mehy.1998.0734","volume":"2","author":"I Guest","year":"1999","unstructured":"Guest I, Uetrecht J . Drugs that induce neutropenia\/agranulocytosis may target specific components of the stromal cell extracellular matrix. Med Hypotheses 1999; 2: 145\u2013151.","journal-title":"Med Hypotheses"},{"key":"BF6500423_CR11","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1097\/01.jcp.0000162814.99818.bb","volume":"25","author":"C Marchesi","year":"2005","unstructured":"Marchesi C, Paini M, Tamborini S, Ampollini P, Maggini C . Recurrence of clozapine-induced agranulocytosis. J Clin Psychopharmacol 2005; 25: 276\u2013277.","journal-title":"J Clin Psychopharmacol"},{"key":"BF6500423_CR12","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1055\/s-2000-8359","volume":"33","author":"M Dettling","year":"2000","unstructured":"Dettling M, Sachse C, Muller-Oerlinghausen B, Roots I, Brockmoller J, Rolfs A et al. Clozapine-induced agranulocytosis and hereditary polymorphisms of clozapine metabolizing enzymes: no association with myeloperoxidase and cytochrome P4502D6. Pharmacopsychiatry 2000; 33: 218\u2013220.","journal-title":"Pharmacopsychiatry"},{"key":"BF6500423_CR13","first-page":"743","volume":"10","author":"KO Price","year":"1991","unstructured":"Price KO . Ethnicity and clozapine-induced agranulocytosis. Clin Pharmacy 1991; 10: 743\u2013744.","journal-title":"Clin Pharmacy"},{"key":"BF6500423_CR14","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1080\/136515001300225231","volume":"5","author":"J Hor\u00e1\u00e8ek","year":"2001","unstructured":"Hor\u00e1\u00e8ek J, Libiger J, H\u00f6schl C, Borzova K, Hendrychov\u00e1 I . Clozapine-induced concordant agranulocytosis in monozygotic twins. Int J Psychiatry Clin Pract 2001; 5: 71\u201373.","journal-title":"Int J Psychiatry Clin Pract"},{"key":"BF6500423_CR15","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/S0165-6147(00)01717-X","volume":"22","author":"M Pirmohamed","year":"2001","unstructured":"Pirmohamed M, Park BK . Genetic susceptibility to adverse drug reactions. Trends Pharmacol Sci 2001; 22: 298\u2013305.","journal-title":"Trends Pharmacol Sci"},{"key":"BF6500423_CR16","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1001\/archpsyc.1990.01810220061007","volume":"47","author":"JA Lieberman","year":"1990","unstructured":"Lieberman JA, Yunis J, Egea E, Canoso RT, Kane JM, Yunis EJ . HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Arch Gen Psychiatry 1990; 47: 945\u2013948.","journal-title":"Arch Gen Psychiatry"},{"key":"BF6500423_CR17","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1182\/blood.V86.3.1177.1177","volume":"86","author":"JJ Yunis","year":"1995","unstructured":"Yunis JJ, Corzo D, Salazar M, Lieberman JA, Howard A, Yunis EJ . HLA associations in clozapine-induced agranulocytosis. Blood 1995; 86: 1177\u20131183.","journal-title":"Blood"},{"issue":"Suppl 1","key":"BF6500423_CR18","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2165\/00002018-199200071-00004","volume":"7","author":"FHJ Claas","year":"1992","unstructured":"Claas FHJ, Abott PA, Witvliet MD, Amaro JD, Barnes PM, Krupp P . No direct clinical relevance of the human leukocyte antigen (HLA\u2212) system in clozapine-induced agranulocytosis. Drug Safety 1992; 7 (Suppl 1): 3\u20136.","journal-title":"Drug Safety"},{"key":"BF6500423_CR19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1001\/archpsyc.58.1.93","volume":"58","author":"M Dettling","year":"2001","unstructured":"Dettling M, Cascorbi I, Roots I, Muller-Oerlinghausen B . Genetic determinants of clozapine-induced agranulocytosis: recent results of HLA\u2212 subtyping in a non-Jewish Caucasian sample. Arch Gen Psychiatry 2001; 58: 93\u201394.","journal-title":"Arch Gen Psychiatry"},{"key":"BF6500423_CR20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1097\/00008571-200103000-00004","volume":"11","author":"M Dettling","year":"2001","unstructured":"Dettling M, Schaub RT, Mueller-Oerlinghausen B, Roots I, Cascorbi I . Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry. Pharmacogenetics 2001; 11: 135\u2013141.","journal-title":"Pharmacogenetics"},{"key":"BF6500423_CR21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1159\/000081453","volume":"58","author":"J Chen","year":"2004","unstructured":"Chen J, Peters U, Foster C, Chatterjee N . A haplotype-based test of association using data from cohort and nested case\u2013control epidemiologic studies. Hum Hered 2004; 58: 18\u201329.","journal-title":"Hum Hered"},{"key":"BF6500423_CR22","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1097\/01.jcp.0000177551.13714.33","volume":"25","author":"I Mosyagin","year":"2005","unstructured":"Mosyagin I, Cascorbi I, Schaub R, Krueger T, Dettling M . Drug-induced agranulocytosis: impact of different Fc\u03b3 receptor polymorphisms? J Clin Psychopharmacol 2005; 25: 435\u2013439.","journal-title":"J Clin Psychopharmacol"},{"key":"BF6500423_CR23","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1023\/A:1014204519468","volume":"22","author":"Z Husain","year":"2002","unstructured":"Husain Z, Levitan E, Larsen CE, Mirza NM, Younes S, Yunis EJ et al. HLA-Cw7 zygosity affects the size of a subset of CD158b+ natural killer cells. J Clin Immunol 2002; 22: 28\u201336.","journal-title":"J Clin Immunol"},{"key":"BF6500423_CR24","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1111\/j.1399-3038.2005.00245.x","volume":"16","author":"L Marin","year":"2005","unstructured":"Marin L, Torio A, Muro M, Fernandez-Parra R, Minguela A, Bosch V et al. Alloimmune neonatal neutropenia and thrombocytopenia associated with maternal anti HNA-1a, HPA-3b, and HLA antibodies. Pediatr Allergy Immunol 2005; 16: 279\u2013282.","journal-title":"Pediatr Allergy Immunol"},{"key":"BF6500423_CR25","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.jneuroim.2005.04.027","volume":"167","author":"E Prat","year":"2005","unstructured":"Prat E, Tomaru U, Sabater L, Park DM, Granger R, Kruse N et al. HLA-DRB5*0101 and -DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype. J Neuroimmunol 2005; 167: 108\u2013119.","journal-title":"J Neuroimmunol"},{"key":"BF6500423_CR26","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1086\/429393","volume":"76","author":"MM Miretti","year":"2005","unstructured":"Miretti MM, Walsh EC, Ke X, Delgado M, Griffiths M, Hunt S et al. A high-resolution linkage-disequilibrium map of the human major histocompatibility complex and first generation of taq single-nucleotide polymorphisms. Am J Hum Genet 2005; 76: 634\u2013646.","journal-title":"Am J Hum Genet"},{"key":"BF6500423_CR27","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/sj.hdy.6800724","volume":"96","author":"SB Piertney","year":"2006","unstructured":"Piertney SB, Oliver MK . The evolutionary ecology of the major histocompatibility complex. Heredity 2006; 96: 7\u201321.","journal-title":"Heredity"},{"key":"BF6500423_CR28","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1046\/j.1399-0039.2003.00133.x","volume":"62","author":"O Ostrousky","year":"2003","unstructured":"Ostrousky O, Meged S, Loewenthal R, Valevski A, Weizman A, Carp H et al. NQO2 gene is associated with clozapine-induced agranulocytosis. Tissue Antigens 2003; 62: 483\u2013491.","journal-title":"Tissue Antigens"},{"key":"BF6500423_CR29","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1097\/01.jcp.0000144891.52858.a6","volume":"24","author":"I Mosyagin","year":"2004","unstructured":"Mosyagin I, Dettling M, Roots I, Mueller-Oerlinghausen B, Cascorbi I . Impact of myeloperoxidase and NADPH-oxidase polymorphisms in drug-induced agranulocytosis. J Clin Psychopharmacol 2004; 24: 613\u2013617.","journal-title":"J Clin Psychopharmacol"},{"key":"BF6500423_CR30","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1097\/01.jcp.0000177668.42640.fe","volume":"25","author":"K Fehsel","year":"2005","unstructured":"Fehsel K, Loeffler S, Krieger K, Henning U, Agelink M, Kolb-Bachofen V et al. Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients. J Clin Psychopharmacol 2005; 25: 419\u2013426.","journal-title":"J Clin Psychopharmacol"},{"key":"BF6500423_CR31","unstructured":"R Development Core Team. R Foundation for Statistical Computing, Version 2.1.1 (2005-06-20), ISBN 3-900051-07-0. 2005."},{"key":"BF6500423_CR32","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1469-1809.1995.tb01608.x","volume":"59","author":"PC Sham","year":"1997","unstructured":"Sham PC, Curtis D . Monte Carlo tests for associations between disease alleles at highly polymorphic loci. Ann Hum Genet 1997; 59: 97\u2013105.","journal-title":"Ann Hum Genet"},{"key":"BF6500423_CR33","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1086\/338688","volume":"70","author":"DJ Schaid","year":"2002","unstructured":"Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA . Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 2002; 70: 425\u2013434.","journal-title":"Am J Hum Genet"},{"key":"BF6500423_CR34","unstructured":"Sinnwell JP, Schaid DJ . Statistical Analysis of Haplotypes with Traits and Covariates when Linkage Phase is Ambiguous, The Haplo.stats Package URL:http:\/\/mayoresearch.mayo.edu\/mayo\/research\/biostat\/schaid.cfm. 2003."},{"key":"BF6500423_CR35","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-3244-0","volume-title":"Generalized Linear Models","author":"P McCullagh","year":"1983","unstructured":"McCullagh P, Nelder JA . Generalized Linear Models. Chapman and Hall: London, 1983."},{"key":"BF6500423_CR36","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1159\/000071811","volume":"55","author":"S Lake","year":"2003","unstructured":"Lake S, Lyon H, Silverman E, Weiss S, Laird N, Schaid D . Estimation and tests of haplotype\u2013environment interaction when linkage phase is ambiguous. Hum Hered 2003; 55: 56\u201365.","journal-title":"Hum Hered"}],"container-title":["The Pharmacogenomics Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/6500423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/6500423","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/6500423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T11:09:59Z","timestamp":1647947399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/6500423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,17]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2007,10,1]]}},"alternative-id":["BF6500423"],"URL":"https:\/\/doi.org\/10.1038\/sj.tpj.6500423","relation":{},"ISSN":["1470-269X","1473-1150"],"issn-type":[{"value":"1470-269X","type":"print"},{"value":"1473-1150","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,17]]},"assertion":[{"value":"13 March 2006","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2006","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2006","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2006","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}