{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:21:29Z","timestamp":1789154489700,"version":"build-2803163510"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially fatal hypersensitivity syndrome with 3% to 10% mortality, and lamotrigine, a first-line treatment for bipolar and seizure disorders, is among the top 5 causative agents of DRESS in the United States and globally. Commercial panels test HLA-B*15:02 and HLA-A*31:01 for risk of carbamazepine-associated severe cutaneous adverse reactions; however, these are not validated for lamotrigine-induced DRESS, and current reports from these commercial assays could therefore provide false reassurance. No\n HLA<\/jats:italic>\n associations with lamotrigine-induced DRESS have been established in US populations.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To identify\n HLA<\/jats:italic>\n genetic variants associated with lamotrigine-induced DRESS in a US population.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This matched case-control study was conducted at 2 US academic medical centers (Vanderbilt University Medical Center and Mass General Brigham). Patients with lamotrigine-induced DRESS confirmed by Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria (score \u22654) were prospectively enrolled between April 2016 and June 2025. Lamotrigine-tolerant controls were matched 10:1 from the Vanderbilt BioVU biobank on sex, self-reported race, and age.\n HLA<\/jats:italic>\n typing included class I (\n HLA-A<\/jats:italic>\n ,\n HLA-B<\/jats:italic>\n , and\n HLA-C<\/jats:italic>\n ) and class II (\n HLA-DPB1<\/jats:italic>\n ,\n HLA-DQA1<\/jats:italic>\n ,\n HLA-DQB1<\/jats:italic>\n , and\n HLA-DRB1<\/jats:italic>\n ) loci for case (high-resolution typing) and control (imputed from genotyping array data) participants.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n HLA<\/jats:italic>\n class I and II alleles and haplotypes were tested using logistic regression with Bonferroni correction for their association with lamotrigine-induced DRESS.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This study included 29 patients with lamotrigine-induced DRESS (case participants; median [IQR] age, 33 [24-56] years; 25 female [86.2%]; 2 Asian [6.9%], 2 Black [6.9%], 23 White [79.3%], and 2 unknown race [6.9%]) and 290 matched control participants. HLA-A*32:01 was associated with lamotrigine-induced DRESS (41.4% [12 case participants] vs 4.1% [12 control participants]; odds ratio [OR], 16.4; 95% CI, 6.4-42.5; Bonferroni-corrected\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). No other alleles or class II loci showed significant associations after correction. The A*32:01\u2009~\u2009B*44:02 haplotype was enriched (OR, 18.4; 95% CI, 4.6-83.8; Bonferroni-corrected\n P<\/jats:italic>\n \u2009=\u2009.001) in lamotrigine-induced DRESS.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this case-control study, HLA-A*32:01 was associated with lamotrigine-induced DRESS in a US population. Given that HLA-A*32:01 is not included in existing commercial pharmacogenomic panels, adding this marker could improve preprescription DRESS risk identification for lamotrigine.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.31291","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:00:33Z","timestamp":1788361233000},"page":"e2631291","source":"Crossref","is-referenced-by-count":1,"title":["HLA-A*32:01 and Lamotrigine-Induced Drug Reaction With Eosinophilia and Systemic Symptoms"],"prefix":"10.1001","volume":"9","author":[{"given":"Matthew S.","family":"Krantz","sequence":"first","affiliation":[{"name":"Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Center for Drug Safety and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Mass General Brigham, Somerville, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Mass General Brigham, Somerville, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Drug Safety and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Gangula","sequence":"additional","affiliation":[{"name":"Center for Drug Safety and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edric A.","family":"Ramirez-Valdez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Mass General Brigham, Somerville, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Blackley","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Mass General Brigham, Somerville, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Ostrov","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danmeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Chopra","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Mallal","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia"},{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Blumenthal","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine, Mass General Brigham, Somerville, Massachusetts"},{"name":"Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Center for Drug Safety and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia"},{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"5","key":"zoi260861r1","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/j.jaip.2022.02.004","article-title":"Drug-induced hypersensitivity syndrome (DIHS)\/drug reaction with eosinophilia and systemic symptoms (DRESS): clinical features and pathogenesis.","volume":"10","author":"Hama","year":"2022","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"3","key":"zoi260861r2","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1111\/1346-8138.12770","article-title":"Sequelae in 145 patients with drug-induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR).","volume":"42","author":"Kano","year":"2015","journal-title":"J Dermatol"},{"issue":"1","key":"zoi260861r3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41572-024-00514-0","article-title":"Severe cutaneous adverse reactions.","volume":"10","author":"Hung","year":"2024","journal-title":"Nat Rev Dis Primers"},{"issue":"2","key":"zoi260861r4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jaci.2022.12.005","article-title":"Updates on the immunopathology and genomics of severe cutaneous adverse drug reactions.","volume":"151","author":"Gibson","year":"2023","journal-title":"J Allergy Clin Immunol"},{"issue":"8","key":"zoi260861r5","doi-asserted-by":"publisher","first-page":"3208","DOI":"10.1016\/j.jaip.2021.05.008","article-title":"Reporting of drug reaction with eosinophilia and systemic symptoms from 2002 to 2019 in the US Food and Drug Administration Adverse Event Reporting System.","volume":"9","author":"Bluestein","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"6982","key":"zoi260861r6","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/428486a","article-title":"Medical genetics: a marker for Stevens-Johnson syndrome.","volume":"428","author":"Chung","year":"2004","journal-title":"Nature"},{"issue":"12","key":"zoi260861r7","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1056\/NEJMoa1013297","article-title":"HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.","volume":"364","author":"McCormack","year":"2011","journal-title":"N Engl J Med"},{"issue":"4","key":"zoi260861r8","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1002\/cpt.1004","article-title":"Clinical pharmacogenetics implementation consortium guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update.","volume":"103","author":"Phillips","year":"2018","journal-title":"Clin Pharmacol Ther"},{"issue":"3","key":"zoi260861r9","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/clpt.2008.89","article-title":"Development of a large-scale de-identified DNA biobank to enable personalized medicine.","volume":"84","author":"Roden","year":"2008","journal-title":"Clin Pharmacol Ther"},{"issue":"8","key":"zoi260861r10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v042.i08","article-title":"MatchIt: nonparametric preprocessing for parametric causal inference.","volume":"42","author":"Ho","year":"2011","journal-title":"J Stat Softw"},{"issue":"2","key":"zoi260861r11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172444","article-title":"Comparison of HLA allelic imputation programs.","volume":"12","author":"Karnes","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"zoi260861r12","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.humimm.2018.09.008","article-title":"Sequence-based HLA-A, B, C, DP, DQ, and DR typing of 496 adults from San Diego, California, USA.","volume":"79","author":"Moore","year":"2018","journal-title":"Hum Immunol"},{"issue":"8016","key":"zoi260861r13","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3.","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"issue":"8","key":"zoi260861r14","doi-asserted-by":"publisher","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings.","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J Chem Inf Model"},{"issue":"D1","key":"zoi260861r15","doi-asserted-by":"publisher","first-page":"D339","DOI":"10.1093\/nar\/gky1006","article-title":"The Immune Epitope Database (IEDB): 2018 update.","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"W1","key":"zoi260861r16","doi-asserted-by":"publisher","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data.","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"zoi260861r17","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/bmb.20966","article-title":"Using the PyMOL application to reinforce visual understanding of protein structure.","volume":"44","author":"Rigsby","year":"2016","journal-title":"Biochem Mol Biol Educ"},{"key":"zoi260861r18","doi-asserted-by":"publisher","journal-title":"PLoS Comput Biol","DOI":"10.1371\/journal.pcbi.1009131"},{"key":"zoi260861r20","doi-asserted-by":"publisher","journal-title":"Stat Med","DOI":"10.1002\/sim.1047"},{"issue":"5","key":"zoi260861r21","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.jmoldx.2019.04.006","article-title":"A rapid allele-specific assay for HLA-A*32:01 to identify patients at risk for vancomycin-induced drug reaction with eosinophilia and systemic symptoms.","volume":"21","author":"Rwandamuriye","year":"2019","journal-title":"J Mol Diagn"},{"issue":"1","key":"zoi260861r22","doi-asserted-by":"publisher","first-page":"200","DOI":"10.14309\/ajg.0000000000002454","article-title":"HLA-B*53:01 is a significant risk factor of liver injury due to phenytoin and other antiepileptic drugs in African Americans.","volume":"119","author":"Nicoletti","year":"2024","journal-title":"Am J Gastroenterol"},{"issue":"1","key":"zoi260861r23","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.jaci.2019.01.045","article-title":"HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms.","volume":"144","author":"Konvinse","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"zoi260861r24","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.phrs.2016.11.027","article-title":"Significant HLA class I type associations with aromatic antiepileptic drug (AED)\u2013induced SJS\/TEN are different from those found for the same AED-induced DRESS in the Spanish population.","volume":"115","author":"Ram\u00edrez","year":"2017","journal-title":"Pharmacol Res"},{"key":"zoi260861r19","unstructured":"Daniel? S, Sinnwell? JP. Haplo.stats: statistical analysis of haplotypes with traits and covariates when linkage phase is ambiguous. Accessed July 20, 2026. https:\/\/CRAN.R-project.org\/package=haplo.stats"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2853517\/krantz_2026_oi_260861_1787752183.50912.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:00:34Z","timestamp":1788361234000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2853517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":24,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.31291","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}