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.
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.
['Somogyi|Andrew A|AA|0000-0003-4779-0380', 'Barratt|Daniel T|DT|0000-0001-6261-353X', 'Phillips|Elizabeth J|EJ|0000-0002-1888-4188', 'Moore|Kylies|K|', 'Ilyas|Fahmida|F|', 'Gabb|Genevieve M|GM|0000-0002-2969-7900']
D000293:Adolescent D000328:Adult D000368:Aged D001315:Australia D000073537:Biological Variation, Population D015331:Cohort Studies D065729:Cytochrome P-450 CYP2C9 D063926:Drug Hypersensitivity Syndrome D005260:Female D005787:Gene Frequency D020022:Genetic Predisposition to Disease D060005:Genotyping Techniques D015235:HLA-B Antigens D006801:Humans D000081034:Indigenous Peoples D008297:Male D008875:Middle Aged D010672:Phenytoin D055815:Young Adult
indigenous Australians drug reaction with eosinophilia and systemic symptoms phenytoin human leucocyte antigen drug toxicity