Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout
Chu Van Son,
Nguyen Thi Hong Loan,
Tran Huyen Trang,
Le Xuan Thinh,
Nguyen Ba Khanh,
Le Thi Hong Nhung,
Nguyen Van Hung,
Tran Ngoc Que,
Nguyen Van Lieu,
Pham Dinh Tung,
Nguyen Thi Van Anh,
Nguyen Dinh Thang
Affiliations
Chu Van Son
Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, Vietnam
Nguyen Thi Hong Loan
Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, Vietnam
Tran Huyen Trang
Department of Internal Medicine, Hanoi Medical University, 1 Ton That Tung, Dong Da, Hanoi 116001, Vietnam
Le Xuan Thinh
Department of Rheumatology, Bach Mai Hospital, 78 Giai Phong, Phuong Mai, Dong Da, Hanoi 116305, Vietnam
Nguyen Ba Khanh
Department of Rheumatology, Bach Mai Hospital, 78 Giai Phong, Phuong Mai, Dong Da, Hanoi 116305, Vietnam
Le Thi Hong Nhung
Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, Vietnam
Nguyen Van Hung
Department of Internal Medicine, Hanoi Medical University, 1 Ton That Tung, Dong Da, Hanoi 116001, Vietnam
Tran Ngoc Que
Stem Cell Bank, National Institute of Hematology and Blood Transfusion, Pham Van Bach, Cau Giay, Hanoi 122000, Vietnam
Nguyen Van Lieu
Department of Neuroscience, Tam Anh General Hospital, 108 Hoang Nhu Tiep, Bo De, Long Bien, Hanoi 125300, Vietnam
Pham Dinh Tung
Department of Probability and Statistics, Faculty of Mathematics-Mechanics-Informatics, VNU University of Science, Vietnam National University, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, Vietnam
Nguyen Thi Van Anh
Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, Vietnam
Nguyen Dinh Thang
Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, Vietnam
Allopurinol (ALP) is commonly used as a drug for gout treatment. However, ALP is known to cause cutaneous adverse reactions (CARs) in patients. The HLA-B*58:01 allele is considered a biomarker of severe CAR (SCAR) in patients with gout, with symptoms of Stevens Johnson syndrome, and with toxic epidermal necrolysis. However, in patients with gout and mild cutaneous adverse drug reactions (MCARs), the role of HLA-allele polymorphisms has not been thoroughly investigated. In this study, 50 samples from ALP-tolerant patients and ALP-induced MCARs patients were genotyped in order to examine the polymorphisms of their HLA-A and HLA-B alleles. Our results showed that the frequencies of HLA-A*02:01/HLA-A*24:02 and HLA-A*02:01/HLA-A*29:01, the dual haplotypes in HLA-A, in patients with ALP-induced MCARs were relatively high, at 33.3% (7/21), which was HLA-B*58:01-independent, while the frequency of these dual haplotypes in the HLA-A locus in ALP-tolerant patients was only 3.45% (1/29). The HLA-B*58:01 allele was detected in 38% (8/21) of patients with ALP-induced MCARs, and in 3.45% (1/29) of ALP-tolerant patients. Notably, although HLA-B*58:01 may be a cause for the occurrence of MCARs in patients with gout, this correlation was not as strong as that previously reported in patients with SCAR. In conclusion, in addition to the HLA-B*58:01 allele, the presence of the dual haplotypes of HLA-A*02:01/HLA-A*24:02 and/or HLA-A*02:01/HLA-A*29:01 in the HLA-A locus may also play an important role in the appearance of ALP-induced MCARs in the Vietnamese population. The obtained primary data may contribute to the development of suitable treatments for patients with gout not only in Vietnam but also in other Asian countries.
