RÉSUMÉ
Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case-control study was performed involving 122 patients with CBZ or allopurinol-induced SCARs and 120 drug tolerant controls. Results:HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion:HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. SNP rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.
Sujet(s)
Allopurinol/effets indésirables , Asiatiques/génétique , Carbamazépine/effets indésirables , Prédisposition génétique à une maladie/génétique , Antigènes HLA-B/génétique , Syndrome de Stevens-Johnson/génétique , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Anticonvulsivants/effets indésirables , Études cas-témoins , Femelle , Prévision , Prédisposition génétique à une maladie/épidémiologie , Antigoutteux/effets indésirables , Humains , Mâle , Adulte d'âge moyen , Indice de gravité de la maladie , Syndrome de Stevens-Johnson/diagnostic , Syndrome de Stevens-Johnson/épidémiologie , Vietnam/épidémiologie , Jeune adulteRÉSUMÉ
Aim: To examine gene expression in different clinical phenotypes of allopurinol-induced severe cutaneous adverse reactions (SCARs). Materials & methods: Gene expression profiling was performed using microarray on 11 RNA samples (four controls, three hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms, four Stevens-Johnson syndrome/toxic epidermal necrolysis) followed by quantitative real-time PCR in a total of 11 SCARs patients and 11 controls. Results: The biological pathways which were significantly enriched in differentially expressed genes in Stevens-Johnson syndrome/toxic epidermal necrolysis compared with hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms patients included; cell surface interactions at the vascular wall, immunoregulatory interactions at the immunological synapse and MyD88 signaling pathways. Overexpression of miR146a occurred in allopurinol-tolerant HLA-B*58:01 carriers. Conclusion: Biological pathways are identified which appear to be implicated in determining clinical phenotypes in allopurinol-induced SCARs. Overexpression of miR146a is potentially important for allopurinol tolerance in HLA-B*58:01 carriers.