Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients



McCormack, M, Gui, Hongsheng, Ingason, Andrés, Speed, Doug, Wright, Galen EB, Zhang, Eunice J, Secolin, Rodrigo, Yasuda, Clarissa, Kwok, Maxwell, Wolking, Stefan
et al (show 2 more authors) (2017) Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients. Neurology, 90 (4).

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Abstract

ObjectiveTo characterize, among European and Han Chinese populations, the genetic predictors ofmaculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepilepticdrugs.MethodsWe conducted a case-control genome-wide association study of autosomal genotypes, in-cluding 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 × 10–11; odds ratio [95%confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium witha missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our resultsreinforce the association betweenHLA-A*31:01and carbamazepine hypersensitivity. We didnot identify significant genetic associations with MPE among Han Chinese patients.ConclusionsThe identification of genetic predictors of MPE in CFHR4 and CFH, members of thecomplement factor H–related protein family, suggest a new link between regulation of thecomplement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 04 Oct 2017 06:32
Last Modified: 30 Nov 2020 15:11
DOI: 10.1212/WNL.0000000000004853
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3009749