Titill: | Genetic variation inCFHpredicts phenytoin-induced maculopapular exanthema in European-descent patients |
Höfundur: |
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Útgáfa: | 2017-12-29 |
Tungumál: | Enska |
Umfang: | e332-e341 |
Háskóli/Stofnun: | Háskóli Íslands University of Iceland |
Svið: | Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) |
Deild: | Læknadeild (HÍ) Faculty of Medicine (UI) |
Birtist í: | Neurology;90(4) |
ISSN: | 0028-3878 1526-632X (eISSN) |
DOI: | 10.1212/WNL.0000000000004853 |
Efnisorð: | Epilepsy; Seizures; Neurology; Case control studies; Antiepileptic drugs; Association studies in genetics; Public health; Flogaveiki; Taugavísindi; Erfðarannsóknir; Lýðheilsa |
URI: | https://hdl.handle.net/20.500.11815/890 |
Tilvitnun:McCormack, M., Gui, H., Ingason, A., Speed, D., Wright, G. E. B., Zhang, E. J., . . . Cavalleri, G. L. (2018). Genetic variation in <em>CFH</em> predicts phenytoin-induced maculopapular exanthema in European-descent patients. Neurology, 90(4), e332-e341. doi:10.1212/wnl.0000000000004853
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Útdráttur: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.
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Athugasemdir:Publisher's version (útgefin grein)
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Leyfi:This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
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