Association of DNA methylation, polymorphism and mRNA level of ALAS1 with antituberculosis drug-induced liver injury.

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics Pub Date : 2024-09-12 DOI:10.1080/14622416.2024.2392480
Zhuolu Hao, Bing Han, Xinyue Zhou, Hongkai Jian, Xiaomin He, Lihuan Lu, Meiling Zhang, Hongqiu Pan, Honggang Yi, Shaowen Tang
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Abstract

Aim: To investigate the association of DNA methylation, genetic polymorphisms and mRNA level of aminolevulinate synthase 1 (ALAS1) with antituberculosis drug-induced liver injury (AT-DILI) risk.Methods: Based on a 1:1 matched case-control study with 182 cases and 182 controls, one CpG island and three single nucleotide polymorphisms (SNPs) were detected. ALAS1 mRNA level was detected in 34 samples.Results: Patients with methylation status were at high risk of AT-DILI (odds ratio: 1.567, 95% CI: 1.015-2.421, p = 0.043) and SNP rs352169 was associated with AT-DILI risk (GA vs. GG, odds ratio: 1.770, 95% CI: 1.101-2.847, p = 0.019). ALAS1 mRNA level in the cases was significantly lower than that in the controls (0.75 ± 0.34 vs. 1.00 ± 0.42, p = 0.021).Conclusion: The methylation status and SNP rs352169 of ALAS1 were associated with AT-DILI risk.

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ALAS1的DNA甲基化、多态性和mRNA水平与抗结核药物引起的肝损伤的关系
目的:研究氨基乙酰丙酸合成酶1(ALAS1)的DNA甲基化、遗传多态性和mRNA水平与抗结核药物性肝损伤(AT-DILI)风险的关系:在182例病例和182例对照的1:1匹配病例对照研究基础上,检测了1个CpG岛和3个单核苷酸多态性(SNPs)。在34个样本中检测了ALAS1 mRNA水平:结果:具有甲基化状态的患者罹患AT-DILI的风险较高(几率比:1.567,95% CI:1.015-2.421,p = 0.043),SNP rs352169与AT-DILI风险相关(GA vs. GG,几率比:1.770,95% CI:1.101-2.847,p = 0.019)。病例中的 ALAS1 mRNA 水平明显低于对照组(0.75 ± 0.34 vs. 1.00 ± 0.42,p = 0.021):结论:ALAS1的甲基化状态和SNP rs352169与AT-DILI风险有关。
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来源期刊
Pharmacogenomics
Pharmacogenomics 医学-药学
CiteScore
3.40
自引率
9.50%
发文量
88
审稿时长
4-8 weeks
期刊介绍: Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.
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