Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

Author:

van Nguyen Dinh1234,Chu Hieu Chi5,Vidal Christopher3,Fulton Richard B4,Nguyen Nguyet Nhu5,Quynh Do Nga Thi6,Tran Tu Linh7,Nguyen Thuy Ninh7,Thu Nguyen Ha Thi8,Chu Hanh Hong9,Thanh Thuc Huyen Thi9,Minh Le Huong Thi9,van Nunen Sheryl310,Anderson Janet4ORCID,Fernando Suran L3410

Affiliation:

1. Vinmec Healthcare System, Hanoi, 100000, Vietnam

2. College of Health Science, VinUniversity, Hanoi, 100000, Vietnam

3. Sydney Medical School - Northern, The University of Sydney, Sydney, 2065, Australia

4. ImmunoRheumatology Laboratory, NSW Health Pathology-North, Royal North Shore Hospital, Sydney, 2065, Australia

5. Center of Allergology & Clinical Immunology, Bach Mai Hospital, Hanoi, 115000, Vietnam

6. Department of Immunology & Molecular Biology, National Institute of Hygiene & Epidemiology, Hanoi, 100000, Vietnam

7. Hanoi Heart Hospital, Hanoi, 100000, Vietnam

8. Department of Allergy & Clinical Immunology, Hanoi Medical University, Hanoi, 100000, Vietnam

9. Department of Allergy, Immunology & Rheumatology, National Hospital of Pediatrics, Hanoi, 100000, Vietnam

10. Department of Clinical immunology & Allergy, Royal North Shore Hospital, Sydney, 2065, Australia

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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