DNA 甲基化、多态性和 ALAS1 mRNA 水平与抗结核药物性肝损伤的关联。
Association of DNA methylation, polymorphism and mRNA level of ALAS1 with antituberculosis drug-induced liver injury.
机构信息
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Department of Internal Medicine, The First Clinical Medical College, Nanjing Medical University, Nanjing, 211166, China.
出版信息
Pharmacogenomics. 2024;25(10-11):451-460. doi: 10.1080/14622416.2024.2392480. Epub 2024 Sep 12.
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. 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. mRNA level was detected in 34 samples. Patients with methylation status were at high risk of AT-DILI (odds ratio: 1.567, 95% CI: 1.015-2.421, = 0.043) and SNP rs352169 was associated with AT-DILI risk (GA vs. GG, odds ratio: 1.770, 95% CI: 1.101-2.847, = 0.019). mRNA level in the cases was significantly lower than that in the controls (0.75 ± 0.34 vs. 1.00 ± 0.42, = 0.021). The methylation status and SNP rs352169 of were associated with AT-DILI risk.
目的
探讨 DNA 甲基化、遗传多态性和 ALAS1 信使 RNA（mRNA）水平与抗结核药物性肝损伤（AT-DILI）风险的关系。方法：采用 1:1 病例对照研究，共纳入 182 例病例和 182 例对照，检测了一个 CpG 岛和三个单核苷酸多态性（SNP）。在 34 例样本中检测了 mRNA 水平。结果：甲基化状态患者发生 AT-DILI 的风险较高（比值比：1.567，95%置信区间：1.015-2.421， = 0.043），SNP rs352169 与 AT-DILI 风险相关（GA 与 GG，比值比：1.770，95%置信区间：1.101-2.847， = 0.019）。病例组的 mRNA 水平明显低于对照组（0.75 ± 0.34 与 1.00 ± 0.42， = 0.021）。结论：ALAS1 的甲基化状态和 SNP rs352169 与 AT-DILI 风险相关。
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