Article (Scientific journals)
Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients.
McCormack, Mark; Gui, Hongsheng; Ingason, Andres et al.
2017In Neurology
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Keywords :
epilepsy; adverse drug reaction; genetics
Abstract :
[en] 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 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. 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.
Disciplines :
Neurology
Author, co-author :
McCormack, Mark
Gui, Hongsheng
Ingason, Andres
Speed, Doug
Wright, Galen E. B.
Zhang, Eunice J.
Secolin, Rodrigo
Yasuda, Clarissa
Kwok, Maxwell
Wolking, Stefan
Becker, Felicitas
Rau, Sarah
Avbersek, Andreja
Heggeli, Kristin
Leu, Costin
Depondt, Chantal
Sills, Graeme J.
Marson, Anthony G.
Auce, Pauls
Brodie, Martin J.
Francis, Ben
Johnson, Michael R.
Koeleman, Bobby P. C.
Striano, Pasquale
Coppola, Antonietta
Zara, Federico
Kunz, Wolfram S.
Sander, Josemir W.
Lerche, Holger
Klein, Karl Martin
Weckhuysen, Sarah
Krenn, Martin
Gudmundsson, Larus J.
Stefansson, Kari
Krause, Roland  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Shear, Neil
Ross, Colin J. D.
Delanty, Norman
Pirmohamed, Munir
Carleton, Bruce C.
Cendes, Fernando
Lopes-Cendes, Iscia
Liao, Wei-Ping
O'Brien, Terence J.
Sisodiya, Sanjay M.
Cherny, Stacey
Kwan, Patrick
Baum, Larry
Cavalleri, Gianpiero L.
More authors (39 more) Less
External co-authors :
yes
Language :
English
Title :
Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients.
Publication date :
29 December 2017
Journal title :
Neurology
ISSN :
1526-632X
Publisher :
Lippincott Williams & Wilkins, United States - Maryland
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
European Projects :
FP7 - 279062 - EPIPGX - Epilepsy Pharmacogenomics: delivering biomarkers for clinical use
Funders :
CE - Commission Européenne [BE]
Commentary :
Copyright (c) 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Available on ORBilu :
since 02 January 2018

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