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High and variable population prevalence of HLA‐B*56:02 in indigenous Australians and relation to phenytoin‐associated drug reaction with eosinophilia and systemic symptoms
Author(s) -
Somogyi Andrew A.,
Barratt Daniel T.,
Phillips Elizabeth J.,
Moore Kylies,
Ilyas Fahmida,
Gabb Genevieve M.
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14025
Subject(s) - phenytoin , indigenous , cyp2c9 , medicine , genotype , human leukocyte antigen , allele , allele frequency , adverse drug reaction , population , hla b , eosinophilia , demography , hla b antigens , drug , immunology , pharmacology , genetics , biology , gene , environmental health , psychiatry , epilepsy , antigen , ecology , sociology
Phenytoin drug reaction with eosinophilia and systemic symptoms (DRESS) in 3 Aboriginal Australians positive for HLA‐B*56:02 has been previously reported. We report the allele frequency of HLA‐B*56:02 in 2 South Australian populations, 1 Aboriginal (4.8%, 95% confidence interval 2.4–7.8%) and the other European (0%). We compared the frequency with publicly available information on HLA‐B*56:02 status in other Indigenous Australian ( n = 4) and European Australian cohorts ( n = 1). In the Indigenous Australian cohorts , HLA‐B*56:02 allele frequency ranged from 1.3 to 19%. We also describe an additional case of phenytoin DRESS (RegiSCAR DRESS score 7) in an Aboriginal Australian that was associated with HLA‐B*56:02 and with CYP2C9*1/*3 genotype. In Aboriginal Australians, phenytoin DRESS appears distinctly linked to HLA‐B*56:02 with an allele carriage rate substantially higher than in Europeans, but also with considerable regional variation. Investigations of human leucocyte antigen and other contributing genes and severe adverse drug reactions in understudied non‐European populations are required to optimize safe medication use and inform risk mitigation strategies.