Genetic Susceptibilities and Prediction Modeling of Carbamazepine and Allopurinol-Induced Severe Cutaneous Adverse Reactions in Vietnamese
Dinh Van Nguyen, Hieu Chi Chu, Christopher Vidal, Richard Fulton, Nguyet Nhu Nguyen, Nga Thi Quynh, Tu Linh Tran, Thuy Ninh Nguyen, Há Thi Nguyen, Hanh Hong Chu, Huyen Thi Thanh Thuc, Huong Thi Le, Sheryl van Nunen, Janet Anderson, Suran L. Fernando
Abstract
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.