1. Polymorphism of IL10, IL4, CTLA4 , and DAO Genes in Cross-Reactive Nonsteroidal Anti-inflammatory Drug Hypersensitivity
- Author
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Andressa Almeida Albuquerque, Greyce Luri Sasahara, Luciana Mabel Ferreira Vasconcelos, Gabrielle Dantheias Barroso, Janaira Fernandes Severo Ferreira, Silvia Helena Barem Rabenhorst, Thereza Lúcia Prata de Almeida, Raphael de Oliveira Rodrigues, Eudiana Vale Francelino, Cynthia Chester Cardoso, and Aparecida Tiemi Nagao-Dias
- Subjects
Adult ,D-Amino-Acid Oxidase ,Male ,Adolescent ,Genotype ,Single-nucleotide polymorphism ,Pharmacology ,Polymorphism, Single Nucleotide ,Drug Hypersensitivity ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Gene Frequency ,Humans ,SNP ,CTLA-4 Antigen ,Pharmacology (medical) ,Allele ,Alleles ,Interleukin 4 ,Aged ,Aged, 80 and over ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,Odds ratio ,Middle Aged ,Molecular biology ,Interleukin-10 ,Interleukin 10 ,030228 respiratory system ,Case-Control Studies ,Female ,Interleukin-4 ,030215 immunology - Abstract
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.
- Published
- 2017