Type

Other / n/a

Authors

Munir Pirmohamed
Gianpiero L Cavalleri
Norman Delanty
Panos Deloukas
David B Goldstein
Sanjay M Sisodiya
Chantal Depondt
B Kevin Park
Werner Pichler
Massimo Pandolfo
and 20 others

Subjects

Psychiatry

Topics
genome wide association study european continental ancestry group single nucleotide polymorphism single nucleotide hla a antigens humans life sciences polymorphism histocompatibility testing genotype exanthema anticonvulsants carbamazepine stevens johnson syndrome drug hypersensitivity

HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. (2011)

Abstract BACKGROUND: Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 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-A*3101 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-A*3101 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-A*3101 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.).
Collections Ireland -> Royal College of Surgeons in Ireland -> Department of Molecular and Cellular Therapeutics
Ireland -> Royal College of Surgeons in Ireland -> Molecular and Cellular Therapeutics Articles

Full list of authors on original publication

Munir Pirmohamed, Gianpiero L Cavalleri, Norman Delanty, Panos Deloukas, David B Goldstein, Sanjay M Sisodiya, Chantal Depondt, B Kevin Park, Werner Pichler, Massimo Pandolfo and 20 others

Experts in our system

1
Gianpiero L Cavalleri
Royal College of Surgeons in Ireland
Total Publications: 35
 
2
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 41
 
3
David B Goldstein
Royal College of Surgeons in Ireland
 
4
Sanjay M Sisodiya
Royal College of Surgeons in Ireland
Total Publications: 13