{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:54:20Z","timestamp":1776682460656,"version":"3.51.2"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004397","name":"Ministry of Public Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (<jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content>s) to severe cutaneous adverse drug reactions (<jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content>s) including drug reactions with eosinophilia and systemic symptoms (<jats:styled-content style=\"fixed-case\">DRESS<\/jats:styled-content>), Stevens\u2010Johnson syndrome (<jats:styled-content style=\"fixed-case\">SJS<\/jats:styled-content>), and toxic epidermal necrolysis (<jats:styled-content style=\"fixed-case\">TEN<\/jats:styled-content>). Drug hypersensitivity has been demonstrated to be associated with variations in the <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> genotypes. This study was to investigate the association between the variations of <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> genotypes and phenobarbital hypersensitivity in Thai children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included <jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content>s. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> genotyping by using a reverse\u2010sequence\u2010specific oligonucleotide (<jats:styled-content style=\"fixed-case\">SSO<\/jats:styled-content>) probes method. The carrier rates of <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content> alleles were compared between 47 cases (27 <jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content>s and 20 <jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content>s) and 54 controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The carrier rates of <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010A*01:01<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010B*13:01<\/jats:italic> were significantly higher in the phenobarbital\u2010induced <jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content>s than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>] 11.66, 95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>] 1.21\u2013578.19; 37.04% vs. 11.11%, p = 0.009, <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 4.60, 95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.29\u201317.98). There was a trend of a higher carrier rate of <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C*06:02<\/jats:italic> in the phenobarbital\u2010induced <jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content>s when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 3.31, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.88\u201313.31). In contrast to the phenobarbital\u2010induced <jats:styled-content style=\"fixed-case\">SCARs<\/jats:styled-content>, only the <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010A*01:01<\/jats:italic> carrier rate in the phenobarbital\u2010induced <jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content>s was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 12.69, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.15\u2013661.62).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>An association between phenobarbital hypersensitivity and <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010A*01:01<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010B*13:01<\/jats:italic> has been demonstrated in Thai children.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13509","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T11:32:50Z","timestamp":1472038370000},"page":"1610-1616","source":"Crossref","is-referenced-by-count":34,"title":["Association of <scp>HLA<\/scp> genotypes with phenobarbital hypersensitivity in children"],"prefix":"10.1111","volume":"57","author":[{"given":"Wiparat","family":"Manuyakorn","sequence":"first","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surakameth","family":"Mahasirimongkol","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Medical Life Sciences Institute Department of Medical Sciences Ministry of Public Health Nonthaburi Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Plernpit","family":"Likkasittipan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wasu","family":"Kamchaisatian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukanya","family":"Wattanapokayakit","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Medical Life Sciences Institute Department of Medical Sciences Ministry of Public Health Nonthaburi Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wimala","family":"Inunchot","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Medical Life Sciences Institute Department of Medical Sciences Ministry of Public Health Nonthaburi Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anannit","family":"Visudtibhan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuanjun","family":"Wichukchinda","sequence":"additional","affiliation":[{"name":"Medical Genetics Center Medical Life Sciences Institute Department of Medical Sciences Ministry of Public Health Nonthaburi Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suwat","family":"Benjaponpitak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2012.705828"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823b478c"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411103311906"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12217"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02533.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01719.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013297"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12564"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.159"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.180"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12058"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2006.07704.x"},{"key":"e_1_2_8_14_1","first-page":"69","volume-title":"Pediatric dermatology","author":"Hamm HJR","year":"2011"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000261917.83337.db"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.04.003"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2010.09.003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213096"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.09.162"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.2340\/00015555-0528","article-title":"HLA\u2010B allele associations with certain drugs are not confirmed in Japanese patients with severe cutaneous drug reactions","volume":"88","author":"Kano Y","year":"2008","journal-title":"Acta Derm Venereol"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02766.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.08.010"},{"key":"e_1_2_8_23_1","first-page":"191","article-title":"HLA\u2010B allele distribution in samples from Thailand National Health Examination Survey","volume":"23","author":"Mahasirimongkol S","year":"2014","journal-title":"J Health Sci"},{"key":"e_1_2_8_24_1","unstructured":"The allele frequency net database 2015. Available at:http:\/\/www.allelefrequencies.net. Accessed March 13 2016."},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2014.04.005"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.13509","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.13509","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.13509","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T12:37:34Z","timestamp":1695559054000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.13509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,24]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/epi.13509"],"URL":"https:\/\/doi.org\/10.1111\/epi.13509","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,24]]}}}