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Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross-Reactive Nonsteroidal Anti-inflammatory Drug Hypersensitivity.

  • Ferreira Vasconcelos, Luciana Mabel1
  • Rodrigues, Raphael de Oliveira1
  • Albuquerque, Andressa Almeida1
  • Barroso, Gabrielle Dantheias1
  • Sasahara, Greyce Luri1
  • Severo Ferreira, Janaira Fernandes2
  • Francelino, Eudiana Vale3
  • Cardoso, Cynthia Chester4
  • Barem Rabenhorst, Silvia Helena5
  • de Almeida, Thereza Lúcia Prata6
  • Nagao-Dias, Aparecida Tiemi1
  • 1 Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal do Ceara, Fortaleza, Brazil. , (Brazil)
  • 2 Department of Pediatric Allergy and Immunology, Hospital Infantil Albert Sabin, Fortaleza, Brazil. , (Brazil)
  • 3 Department of Pharmacy, Faculty of Pharmacy, Universidade Federal do Ceara, Fortaleza, Brazil. , (Brazil)
  • 4 Laboratório de Virologia Molecular, Department of Genetics, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. , (Brazil)
  • 5 Laboratory of Molecular Genetics, Department of Pathology and Forensic Medicine, Universidade Federal do Ceara, Fortaleza, Brazil. , (Brazil)
  • 6 Department of Dermatology, Hospital Universitario Walter Cantidio, Universidade Federal do Ceara, Fortaleza, Brazil. , (Brazil)
Published Article
Journal of clinical pharmacology
Publication Date
Jul 27, 2017
DOI: 10.1002/jcph.986
PMID: 28750137


Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory drugs. Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction-restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG genotype (P = .04 for the codominant model), suggesting an allele dose effect. The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR values, suggesting independent effects for both SNPs. The results are striking. In conclusion, these results suggest that polymorphisms in regulatory targets of the immune response and in DAO gene could modulate an individual's susceptibility to nonsteroidal anti-inflammatory drug hypersensitivity reactions. Further studies will be necessary to complement our results.

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