TY  - JOUR
JF  - Neurology
A1  - McCormack, M
A1  - Gui, H
A1  - Ingason, A
A1  - Speed, D
A1  - Wright, GEB
A1  - Zhang, EJ
A1  - Secolin, R
A1  - Yasuda, C
A1  - Kwok, M
A1  - Wolking, S
A1  - Becker, F
A1  - Rau, S
A1  - Avbersek, A
A1  - Heggeli, K
A1  - Leu, C
A1  - Depondt, C
A1  - Sills, GJ
A1  - Marson, AG
A1  - Auce, P
A1  - Brodie, MJ
A1  - Francis, B
A1  - Johnson, MR
A1  - Koeleman, BPC
A1  - Striano, P
A1  - Coppola, A
A1  - Zara, F
A1  - Kunz, WS
A1  - Sander, JW
A1  - Lerche, H
A1  - Klein, KM
A1  - Weckhuysen, S
A1  - Krenn, M
A1  - Gudmundsson, LJ
A1  - Stefánsson, K
A1  - Krause, R
A1  - Shear, N
A1  - Ross, CJD
A1  - Delanty, N
A1  - EPIGEN Consortium, .
A1  - Pirmohamed, M
A1  - Carleton, BC
A1  - Canadian Pharmacogenomics Network for Drug Safety, .
A1  - Cendes, F
A1  - Lopes-Cendes, I
A1  - Liao, W-P
A1  - O'Brien, TJ
A1  - Sisodiya, SM
A1  - EpiPGX Consortium, .
A1  - Cherny, S
A1  - Kwan, P
A1  - Baum, L
A1  - ILAE-CGC, .
A1  - Cavalleri, GL
ID  - discovery10041504
N2  - 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.
SN  - 1526-632X
UR  - https://doi.org/10.1212/WNL.0000000000004853
N1  - 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.
IS  - 4
TI  - Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients
EP  - e341
AV  - public
SP  - e332
VL  - 90
Y1  - 2018/01/23/
ER  -