Journal article
Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients
Mark McCormack, Hongsheng Gui, Andres Ingason, Doug Speed, Galen EB Wright, Eunice J Zhang, Rodrigo Secolin, Clarissa Yasuda, Maxwell Kwok, Stefan Wolking, Felicitas Becker, Sarah Rau, Andreja Avbersek, Kristin Heggeli, Costin Leu, Chantal Depondt, Graeme J Sills, Anthony G Marson, Pauls Auce, Martin J Brodie Show all
NEUROLOGY | LIPPINCOTT WILLIAMS & WILKINS | Published : 2018
Abstract
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 i..
View full abstractGrants
Awarded by European Commission (7th Framework Programme)
Awarded by Science Foundation Ireland
Awarded by RCSI seed funding grant
Awarded by General Research Funds from Hong Kong
Awarded by Health and Medical Research Fund from Hong Kong
Awarded by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil
Awarded by Canadian Institutes of Health Research (CIHR) Drug Safety and Effectiveness Network
Awarded by Medical Research Council
Funding Acknowledgements
This study was not industry-sponsored. The work was supported by a grant from the European Commission (7th Framework Programme Grant 279062, EpiPGX). M.M.C. and G.L.C. are supported by Science Foundation Ireland, grant 13/CDA/2223, and an RCSI seed funding grant GA 14-1899. This project was supported by the General Research Funds (HKU7623/08M and HKU7747/07M to S.C., CUHK4466/06M to P.K.) and Health and Medical Research Fund (HMRF 01120086 to P.K.) from Hong Kong. Some results presented in this article were prepared using the HPC facilities of the University of Luxembourg. This work was partly undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme (J.W.S., S.M.S.). The work was also supported by the Epilepsy Society, UK (J.W.S., S.M.S.), by the foundation "no epilep," the German Chapter of the ILAE (DGfE) (both to H.L.). F.C. and I. L.-C. are supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil, through grant 2013/07559-3. J.E.Z. and M.P. thank the NHS Chair of Pharmacogenetics programme and MRC Centre for Drug Safety Science for support in Liverpool. B.C.C. and C.J.D.R. are supported by the Canadian Institutes of Health Research (CIHR) Drug Safety and Effectiveness Network (FRN-117588), the Canada Foundation for Innovation and the Canadian Dermatology Foundation. G.E.B.W. is supported by a CIHR Fellowship. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. M.M.C., H.G., and G.L.C. had full access to all the data in the study and the corresponding authors had final responsibility for the decision to submit for publication.