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HLA alleles and antiseizure medication-induced cutaneous reactions in Brazil: A case-control study.
Spina Tensini, Tallulah; de Paola, Luciano; Boldt, Angelica Beate Winter; Glehn, Cristina de Queiroz Carrascosa Von; Bettinotti, Maria; Silvado, Carlos Eduardo Soares.
Afiliação
  • Spina Tensini T; Neurology Department, Federal University of Paraná, Curitiba, Brazil.
  • de Paola L; Neurology Department, Federal University of Paraná, Curitiba, Brazil.
  • Boldt ABW; Postgraduate Program in Genetics, Federal University of Paraná, Curitiba, Brazil.
  • Glehn CQCV; Immunogenetics Laboratory, Cajuru University Hospital, Curitiba, Brazil.
  • Bettinotti M; Immunogenetics Laboratory, Johns Hopkins University, Baltimore, Maryland, USA.
  • Silvado CES; Neurology Department, Federal University of Paraná, Curitiba, Brazil.
HLA ; 102(3): 269-277, 2023 09.
Article em En | MEDLINE | ID: mdl-37002612
In this observational case-control study, 107 cutaneous adverse reaction (CAR) cases (CAR+) manifesting up to 12 weeks after the start of treatment with antiseizure medication (ASM) were identified. Control groups consisted of 98 epilepsy patients without a history of CAR (CAR-) and 3965 healthy individuals in the Brazilian National Registry of Bone Marrow Donors. All participants were HLA typed by high-resolution Next Generation Sequencing for HLA-A, B, C, DQB1 and DRB1; HLA-DPA1, DPB1, DQA1, DRB3, DRB4 and DRB5 were also sequenced in samples from CAR+ and CAR- individuals. The relationship between the carrier frequency of each allele, CAR type and ASM for all participants was investigated. The ASMs most frequently associated with CAR were carbamazepine (48% of CAR+ subjects), lamotrigine (23%), phenytoin (18%), phenobarbital (13%) and oxcarbazepine (5%). The main alleles associated with a risk of CAR were HLA-A*02:05 (OR = 6.28; p = 0.019, carbamazepine or oxcarbazepine); HLA-DPA1*02:02 (OR = 4.16, p = 0.003, carbamazepine); HLA-B*53:01 (OR = 47.9, p = 0.014, oxcarbazepine), HLA-DPA1*03:01/DPB1*105:01 (OR = 25.7, p = 0.005, phenobarbital); HLA-C*02:10 (OR = 25.7, p = 0.005, phenobarbital) and HLA-DRB1*04:02 (OR = 17.22, p = 0.007, phenytoin). HLA-A*03:01 increased the risk for phenytoin-induced maculopapular exanthema 4.71-fold (p = 0.009), and HLA-B*35:02 was associated with a 25.6-fold increase in the risk of carbamazepine-induced Stevens-Johnson syndrome (p = 0.005). None of the 4170 subjects carried the HLA-B*15:02 allele, and HLA-A*31:01 was not associated with CAR. Hence, HLA-A*31:01 and HLA-B*15:02 were not associated with CAR in this population. Although other HLA class I and II alleles tested were associated with a risk of CAR, none of these associations were strong enough to warrant HLA testing before prescribing ASM.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenitoína / Antígenos HLA-B Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: HLA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenitoína / Antígenos HLA-B Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: HLA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido