%0 Journal Article
%@ 1526-632X
%A McCormack, M
%A Gui, H
%A Ingason, A
%A Speed, D
%A Wright, GEB
%A Zhang, EJ
%A Secolin, R
%A Yasuda, C
%A Kwok, M
%A Wolking, S
%A Becker, F
%A Rau, S
%A Avbersek, A
%A Heggeli, K
%A Leu, C
%A Depondt, C
%A Sills, GJ
%A Marson, AG
%A Auce, P
%A Brodie, MJ
%A Francis, B
%A Johnson, MR
%A Koeleman, BPC
%A Striano, P
%A Coppola, A
%A Zara, F
%A Kunz, WS
%A Sander, JW
%A Lerche, H
%A Klein, KM
%A Weckhuysen, S
%A Krenn, M
%A Gudmundsson, LJ
%A Stefánsson, K
%A Krause, R
%A Shear, N
%A Ross, CJD
%A Delanty, N
%A EPIGEN Consortium, .
%A Pirmohamed, M
%A Carleton, BC
%A Canadian Pharmacogenomics Network for Drug Safety, .
%A Cendes, F
%A Lopes-Cendes, I
%A Liao, W-P
%A O'Brien, TJ
%A Sisodiya, SM
%A EpiPGX Consortium, .
%A Cherny, S
%A Kwan, P
%A Baum, L
%A ILAE-CGC, .
%A Cavalleri, GL
%D 2018
%F discovery:10041504
%J Neurology
%N 4
%P e332-e341
%T Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients
%U https://discovery.ucl.ac.uk/id/eprint/10041504/
%V 90
%X 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*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.
%Z Copyright © 2017 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.