HLA-DQB1*05:02 Allele Association with Anti-Tuberculosis Drug Induced Liver Injury: A Single-Hospital Based Study in Jakarta, Indonesian Population

Kinasih Prayuni, Hilyatuz Zahroh, Syafrizal Syafrizal, Rika Yuliwulandari
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Abstract

Past studies have delved into the genetic factors underlying anti-tuberculosis drug-induced liver injury (AT-DILI), primarily concentrating on polymorphisms in genes responsible for drug-metabolizing enzymes. However, the immune system's potential impact on drug adverse effects, specifically through genes such as HLA, has received limited attention. Previous research has notably revealed an association between HLA-DQB1*05 and AT-DILI, specifically the prevalence of the HLA-DQB*05:02 allele in AT-DILI patients. In light of this, our study aimed to investigate a potential link between HLA-DQB1*05:02 alleles and AT-DILI. In this study, we included 51 AT-DILI cases and 59 controls belonging to the Javanese ethnic group. The HLA-DQB1*05:02 genotypes were determined using a customized PCR-based typing method, and the results were further confirmed by analyzing five samples via the Luminex assay. Our findings revealed a significant association between HLA-DQA1*05: 02 and the risk of AT-DILI (P = 0.022; OR (95% CI) = 6.11 (1.25-29.74)). Moreover, the consistent results obtained from the Luminex assay validated the reliability of the custom PCR-based genotyping approach. This preliminary study sheds light on the relationship between the HLA-DQB1*05:02 allele and AT-DILI within the Indonesian population. Furthermore, our study demonstrates the dependability of custom PCR-based genotyping in detecting HLA-DQB1*05:02 alleles. Nevertheless, further research is imperative to corroborate and expand upon our findings.
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HLA-DQB1*05:02等位基因与抗结核药物引起的肝损伤相关:一项基于印度尼西亚雅加达人群的单医院研究
过去的研究已经深入研究了抗结核药物性肝损伤(AT-DILI)的遗传因素,主要集中在负责药物代谢酶的基因多态性上。然而,免疫系统对药物不良反应的潜在影响,特别是通过HLA等基因,受到的关注有限。先前的研究已经显著揭示了HLA-DQB1*05与AT-DILI之间的关联,特别是HLA-DQB*05:02等位基因在AT-DILI患者中的患病率。鉴于此,我们的研究旨在探讨HLA-DQB1*05:02等位基因与AT-DILI之间的潜在联系。在这项研究中,我们纳入了51例AT-DILI病例和59例属于爪哇族的对照。采用定制的pcr分型方法确定HLA-DQB1*05:02基因型,并通过Luminex assay对5份样品进行分析,进一步确认结果。我们的研究结果显示HLA-DQA1* 0.05: 02与AT-DILI风险显著相关(P = 0.022;或(95% ci) = 6.11(1.25-29.74))。此外,从Luminex检测中获得的一致结果验证了基于pcr的定制基因分型方法的可靠性。本初步研究揭示了印度尼西亚人群中HLA-DQB1*05:02等位基因与AT-DILI之间的关系。此外,我们的研究证明了基于定制pcr的基因分型检测HLA-DQB1*05:02等位基因的可靠性。然而,进一步的研究是必要的,以证实和扩大我们的发现。
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