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Association of HLA genotypes with phenobarbital hypersensitivity in children
Author(s) -
Manuyakorn Wiparat,
Mahasirimongkol Surakameth,
Likkasittipan Plernpit,
Kamchaisatian Wasu,
Wattanapokayakit Sukanya,
Inunchot Wimala,
Visudtibhan Anannit,
Wichukchinda Nuanjun,
Benjaponpitak Suwat
Publication year - 2016
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13509
Subject(s) - toxic epidermal necrolysis , phenobarbital , medicine , odds ratio , confidence interval , immunology , genotype , delayed hypersensitivity , gastroenterology , dermatology , biology , antigen , genetics , gene
Summary Objective Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes ( MP s) to severe cutaneous adverse drug reactions ( SCAR s) including drug reactions with eosinophilia and systemic symptoms ( DRESS ), Stevens‐Johnson syndrome ( SJS ), and toxic epidermal necrolysis ( TEN ). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. Methods The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCAR s and MP 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 HLA genotyping by using a reverse‐sequence‐specific oligonucleotide ( SSO ) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCAR s and 20 MP s) and 54 controls. Results The carrier rates of HLA ‐A*01:01 and HLA ‐B*13:01 were significantly higher in the phenobarbital‐induced SCAR s than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [ OR ] 11.66, 95% confidence interval [ CI ] 1.21–578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95% CI 1.29–17.98). There was a trend of a higher carrier rate of HLA ‐C*06:02 in the phenobarbital‐induced SCAR s when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88–13.31). In contrast to the phenobarbital‐induced SCARs , only the HLA ‐A*01:01 carrier rate in the phenobarbital‐induced MP s was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15–661.62). Significance An association between phenobarbital hypersensitivity and HLA ‐A*01:01 and HLA ‐B*13:01 has been demonstrated in Thai children.