Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout

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<sup>*</sup>58:01 allele is considered a biomarker of severe CAR (SCAR) in patients with gout, with symptoms of Stevens Johnson syndrom...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/11/9/1611
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author 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
author_facet 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
author_sort Chu Van Son
collection DOAJ
description 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<sup>*</sup>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<sup>*</sup>02:01/HLA-A<sup>*</sup>24:02 and HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>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<sup>*</sup>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<sup>*</sup>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<sup>*</sup>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<sup>*</sup>58:01 allele, the presence of the dual haplotypes of HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>24:02 and/or HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>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.
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spelling doaj.art-10e5ab8184c542f9ac03fd60439090582023-11-22T12:39:41ZengMDPI AGDiagnostics2075-44182021-09-01119161110.3390/diagnostics11091611Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with GoutChu Van Son0Nguyen Thi Hong Loan1Tran Huyen Trang2Le Xuan Thinh3Nguyen Ba Khanh4Le Thi Hong Nhung5Nguyen Van Hung6Tran Ngoc Que7Nguyen Van Lieu8Pham Dinh Tung9Nguyen Thi Van Anh10Nguyen Dinh Thang11Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, VietnamKey Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, VietnamDepartment of Internal Medicine, Hanoi Medical University, 1 Ton That Tung, Dong Da, Hanoi 116001, VietnamDepartment of Rheumatology, Bach Mai Hospital, 78 Giai Phong, Phuong Mai, Dong Da, Hanoi 116305, VietnamDepartment of Rheumatology, Bach Mai Hospital, 78 Giai Phong, Phuong Mai, Dong Da, Hanoi 116305, VietnamKey Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, VietnamDepartment of Internal Medicine, Hanoi Medical University, 1 Ton That Tung, Dong Da, Hanoi 116001, VietnamStem Cell Bank, National Institute of Hematology and Blood Transfusion, Pham Van Bach, Cau Giay, Hanoi 122000, VietnamDepartment of Neuroscience, Tam Anh General Hospital, 108 Hoang Nhu Tiep, Bo De, Long Bien, Hanoi 125300, VietnamDepartment of Probability and Statistics, Faculty of Mathematics-Mechanics-Informatics, VNU University of Science, Vietnam National University, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, VietnamKey Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, VietnamKey Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi, 334 Nguyen Trai, Thanh Xuan, Hanoi 120017, VietnamAllopurinol (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<sup>*</sup>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<sup>*</sup>02:01/HLA-A<sup>*</sup>24:02 and HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>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<sup>*</sup>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<sup>*</sup>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<sup>*</sup>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<sup>*</sup>58:01 allele, the presence of the dual haplotypes of HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>24:02 and/or HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>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.https://www.mdpi.com/2075-4418/11/9/1611goutallopurinolmild cutaneous adverse drug reactions (MCARs)HLA-B<sup>*</sup>58:01 alleleone-locus haplotypesHLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>24:02
spellingShingle 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
Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout
Diagnostics
gout
allopurinol
mild cutaneous adverse drug reactions (MCARs)
HLA-B<sup>*</sup>58:01 allele
one-locus haplotypes
HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>24:02
title Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout
title_full Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout
title_fullStr Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout
title_full_unstemmed Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout
title_short Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout
title_sort predominant hla alleles and haplotypes in mild adverse drug reactions caused by allopurinol in vietnamese patients with gout
topic gout
allopurinol
mild cutaneous adverse drug reactions (MCARs)
HLA-B<sup>*</sup>58:01 allele
one-locus haplotypes
HLA-A<sup>*</sup>02:01/HLA-A<sup>*</sup>24:02
url https://www.mdpi.com/2075-4418/11/9/1611
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