Next-generation sequencing-based HLA typing reveals the association of HLA-B*46:01:01 and HLA-DRB1*09:01:02 alleles with carbamazepine-induced hypersensitivity reactions in Vietnamese patients with epilepsy

Bui, Thao Phuong; Nguyen, Linh Thi Tu; Le, Phuong Lan; Le, Nhan Thi Thanh; Nguyen, Thuy Doan; Nguyen, Lieu Van; Nguyen, Anh Thi Van; Trinh, Thai Hong

doi:10.1016/j.humimm.2023.01.005

Cited by 2 publications

(4 citation statements)

References 26 publications

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“…Surprisingly, no eligible studies conducted in the southern region of Vietnam were identified or included in this meta-analysis ( Supplementary Table S1 ). Interestingly, a recent study by Bui TP et al ( Bui et al, 2023 ) reported a negative association between HLA-*B15:02 and SCARs in Vietnamese in January 2023. However, our analysis using pooled data from all six studies showed a strong positive association between HLA-B*15:02 and SCARs, as determined by both common effect and random effects models ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 98%

“…A meta-analysis was performed about the risk of HLA-B*15:02 and SCARs in Vietnamese with a total of 6 studies ( Van Nguyen et al, 2015 ; Van Nguyen et al, 2017 ; Huyen et al, 2020 ; van Nguyen et al, 2021 ; Chu, 2022 ; Bui et al, 2023 ). All these 6 studies were conducted and recruited patients exclusively in the northern region of Vietnam, specifically at Bach Mai Hospital, Tam Anh Hospital (Ha Noi branch), and the National Hospital of Dermatology and Venerology.…”

Section: Resultsmentioning

confidence: 99%

“…In the population of Southern Vietnamese, our study reported a higher frequency of the HLA-B*15:02 allele, 20% compared to 11.88% in a study of the general population of Southern Vietnamese by Do MD et al ( Do et al, 2020 ). In the population of Northern Vietnamese, the frequency of HLA-B*15:02 in epileptic patients varies between studies 13.5% ( Van Nguyen et al, 2015 ), 15.2% ( van Nguyen et al, 2021 ), 17.7% ( Bui et al, 2023 ), and 41.7% ( Huyen et al, 2020 ). The possible explanation may be due to the different regions or the small sample size, which can only reflect a part of the whole population.…”

Section: Discussionmentioning

confidence: 99%

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The pharmacogenomics of carbamazepine-induced cutaneous adverse drug reaction in the South of Vietnam

et al. 2023

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Background: The relationship between HLA-B*15:02 and Severe Cutaneous Adverse Reactions was rigorously examined in Japanese, Han Chinese, Thais, and Caucasians. However, the number of studies about this topic in Vietnamese population is still limited and mostly focuses on the North of Vietnam.Objective: This study aims to clarify the genetic culprit of SCARs in Vietnamese population, particularly in the South of Vietnam, and to validate our result by a meta-analysis about this topic in Vietnamese.Method: A retrospective case-control study with 37 patients treated with carbamazepine monotherapy. Statistical calculation and meta-analysis were performed by R software.Result:HLA-B*15:02 increases the risk of SJS 12.5 times higher in CBZ-treated patients (p-value = 0.017). However, this allele has no impact on MCARs (Mild Cutaneous Adverse Reactions) of CBZ. The number needed to test and the number needed to genotype is two and nine patients respectively.Conclusion: This study recommends more investigations about the cost-effectiveness of this test to accelerate the protection of Southern Vietnamese from SCARs.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The pharmacogenomics of carbamazepine-induced cutaneous adverse drug reaction in the South of Vietnam

et al. 2023

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“…Tiêu chuẩn loại trừ: i) Bệnh nhân có tình trạng dị ứng trên lâm sàng trước khi dùng thuốc hoặc tình trạng dị ứng xuất hiện trong vòng 24 giờ sau khi sử dụng thuốc; ii) Phụ nữ đang mang thai; iii) Bệnh nhân không đủ xét nghiệm cần thiết cho nghiên cứu; iv) Bệnh nhân từ chối tham gia nghiên cứu. Thông tin chi tiết về các đặc điểm bệnh học của đối tượng nghiên cứu đã được mô tả trong công bố của nhóm nghiên cứu trên cùng đối tượng bệnh nhân [12].…”

Section: Vật Liệuunclassified

Large-Scale Deletions of Mitochondrial DNA in Epilepsy Patients Treated with Carbamazepine

Thi Tu Linh,

Huong,

Nhan

et al. 2024

NST

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Mitochondrial dysfunction, caused by large-scale deletion mutations, can lead to impaired function of the mitochondrial respiratory chain, reduced ATP production, and serious effects on most energy-consuming organs, such as neurons, and can induce seizures in epilepsy. Carbamazepine (CBZ), the first-line drug used in the treatment of epilepsy, can be harmful to mitochondria and its side effects may be related to mitochondrial dysfunction. In this study, mitochondrial DNA (mtDNA) large-scale deletions were identified in 65 CBZ-treated patients with epilepsy, including 32 patients with CBZ-induced hypersensitivity and 33 with CBZ tolerance. Using the PCR method, mtDNA large-scale deletions were identified in 21/65 epilepsy patients (32.31%), including 9/32 CBZ-hypersensitivity patients (28.13%) and 12/33 CBZ-tolerance patients (36.36%). However, this difference was not statistically significant. The “common deletion” of 4977 bp was the most prevalent deletion. Remarkably, the new deletion of 4876 bp in a CBZ-tolerance patient was reported for the first time. Quantitative PCR analysis showed that the level of mtDNA large-scale deletion was significantly lower in the hypersensitivity group than in the tolerance group (p < 0.05). Besides, analysis of the association between the level of mtDNA large-scale deletion and mtDNA copy number with the clinical features of CBZ hypersensitivity patients showed no relationship with age and severity of skin lesions (p > 0.05). However, there was a statistically significant association between the level of mtDNA large-scale deletions and sex (p < 0.01). Further studies are needed to evaluate the role of mtDNA large-scale deletions in epilepsy and their association with antiepileptic drugs.

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Next-generation sequencing-based HLA typing reveals the association of HLA-B46:01:01 and HLA-DRB109:01:02 alleles with carbamazepine-induced hypersensitivity reactions in Vietnamese patients with epilepsy

Cited by 2 publications

References 26 publications

The pharmacogenomics of carbamazepine-induced cutaneous adverse drug reaction in the South of Vietnam

The pharmacogenomics of carbamazepine-induced cutaneous adverse drug reaction in the South of Vietnam

Large-Scale Deletions of Mitochondrial DNA in Epilepsy Patients Treated with Carbamazepine

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