Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients.
Neurology
; 90(4): e332-e341, 2018 01 23.
Article
em En
| MEDLINE
| ID: mdl-29288229
ABSTRACT
OBJECTIVE:
To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs.METHODS:
We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed.RESULTS:
We report an association between a rare variant in the complement factor H-related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 × 10-11; odds ratio [95% confidence interval] 7 [3.2-16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*3101 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients.CONCLUSIONS:
The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H-related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas
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Fenitoína
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Variação Genética
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Toxidermias
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Anticonvulsivantes
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article