Imperial College London

ProfessorMichaelJohnson

Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine
 
 
 
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Contact

 

m.johnson Website

 
 
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Location

 

E419Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{McCormack:2011,
author = {McCormack, M and Alfirevic, A and Bourgeois, S and Farrell, JJ and Kasperaviciute, D and Carrington, MN and Sills, G and Marson, A and Jla, X and de, Bakker PI and Chinthapalli, K and Molokhia, M and Johnson, MR and O'Connor, GD and Chalia, E and Alhusaini, S and Shianna, KV and Radtke, RA and Heinzen, EL and Walley, N and Pandolfo, M and Pichler, W and Park, BK and Depondt, C and Sisodiya, SM and Goldstein, DB and Deloukas, P and Delanty, N and Cavaller, GL and Pirmohamed, M},
journal = {N Engl J Med 2011},
pages = {1134--1143},
title = {HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.},
volume = {364},
year = {2011}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - AbstractBACKGROUND: Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.METHODS: We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions.RESULTS: The HLA-A3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P=3.5×10(-8)). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A3101 allele (P=1.1×10(-6)). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS-TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18).CONCLUSIONS: The presence of the HLA-A3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. (Funded by the U.K. Department of Health and others.).
AU - McCormack,M
AU - Alfirevic,A
AU - Bourgeois,S
AU - Farrell,JJ
AU - Kasperaviciute,D
AU - Carrington,MN
AU - Sills,G
AU - Marson,A
AU - Jla,X
AU - de,Bakker PI
AU - Chinthapalli,K
AU - Molokhia,M
AU - Johnson,MR
AU - O'Connor,GD
AU - Chalia,E
AU - Alhusaini,S
AU - Shianna,KV
AU - Radtke,RA
AU - Heinzen,EL
AU - Walley,N
AU - Pandolfo,M
AU - Pichler,W
AU - Park,BK
AU - Depondt,C
AU - Sisodiya,SM
AU - Goldstein,DB
AU - Deloukas,P
AU - Delanty,N
AU - Cavaller,GL
AU - Pirmohamed,M
EP - 1143
PY - 2011///
SP - 1134
TI - HLA-A3101 and carbamazepine-induced hypersensitivity reactions in Europeans.
T2 - N Engl J Med 2011
VL - 364
ER -