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

Publication ,  Journal Article
McCormack, M; Alfirevic, A; Bourgeois, S; Farrell, JJ; Kasperavičiūtė, D; Carrington, M; Sills, GJ; Marson, T; Jia, X; de Bakker, PIW; Park, BK ...
Published in: N Engl J Med
March 24, 2011

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.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

March 24, 2011

Volume

364

Issue

12

Start / End Page

1134 / 1143

Location

United States

Related Subject Headings

  • White People
  • Stevens-Johnson Syndrome
  • Polymorphism, Single Nucleotide
  • Humans
  • Histocompatibility Testing
  • HLA-A Antigens
  • Genotype
  • Genome-Wide Association Study
  • General & Internal Medicine
  • Exanthema
 

Citation

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McCormack, M., Alfirevic, A., Bourgeois, S., Farrell, J. J., Kasperavičiūtė, D., Carrington, M., … Pirmohamed, M. (2011). HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med, 364(12), 1134–1143. https://doi.org/10.1056/NEJMoa1013297
McCormack, Mark, Ana Alfirevic, Stephane Bourgeois, John J. Farrell, Dalia Kasperavičiūtė, Mary Carrington, Graeme J. Sills, et al. “HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.N Engl J Med 364, no. 12 (March 24, 2011): 1134–43. https://doi.org/10.1056/NEJMoa1013297.
McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiūtė D, Carrington M, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011 Mar 24;364(12):1134–43.
McCormack, Mark, et al. “HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.N Engl J Med, vol. 364, no. 12, Mar. 2011, pp. 1134–43. Pubmed, doi:10.1056/NEJMoa1013297.
McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiūtė D, Carrington M, Sills GJ, Marson T, Jia X, de Bakker PIW, Chinthapalli K, Molokhia M, Johnson MR, O’Connor GD, Chaila E, Alhusaini S, Shianna KV, Radtke RA, Heinzen EL, Walley N, Pandolfo M, Pichler W, Park BK, Depondt C, Sisodiya SM, Goldstein DB, Deloukas P, Delanty N, Cavalleri GL, Pirmohamed M. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011 Mar 24;364(12):1134–1143.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

March 24, 2011

Volume

364

Issue

12

Start / End Page

1134 / 1143

Location

United States

Related Subject Headings

  • White People
  • Stevens-Johnson Syndrome
  • Polymorphism, Single Nucleotide
  • Humans
  • Histocompatibility Testing
  • HLA-A Antigens
  • Genotype
  • Genome-Wide Association Study
  • General & Internal Medicine
  • Exanthema