Publication
Title
Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients
Author
Institution/Organisation
EPIGEN Consortium
Canadian Pharmacogenomics Network
for the EpiPGX Consortium
Int League Epilepsy Consortium
Abstract
ObjectiveTo characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs.MethodsWe 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.ResultsWe 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 x 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*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients.ConclusionsThe 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.
Language
English
Source (journal)
Neurology / American Academy of Neurology. - Minneapolis, Minn
Publication
Minneapolis, Minn : 2018
ISSN
0028-3878
Volume/pages
90:4(2018), p. E332-+
ISI
000427799500009
Pubmed ID
29288229
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 04.05.2018
Last edited 15.07.2021
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