HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans  

Oleh:

McCormack, Mark ; Alfirevic, Ana ; Bourgeois, Stephane ; Farrell, John J.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The New England Journal of Medicine (keterangan: ada di Proquest) vol. 364 no. 12 (Mar. 2011), page 1134-1143.
Topik: Hypersensitivity; Maculopapular Exanthema; HLA-A*3101

Ketersediaan

Perpustakaan FK Nomor Panggil: N08.K.2011.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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%.

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