Department of Laboratory Medicine, Chengdu Second People's Hospital, Chengdu, China; Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Department of Respiratory and Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Ann Palliat Med. 2021 Nov;10(11):11733-11744. doi: 10.21037/apm-21-2924.
The most serious and common complication of the medication recommended by World Health Organization (WHO) for tuberculosis (TB) is anti-tuberculosis drugs-induced hepatotoxicity (ATDH). Pregnane X receptor (PXR) is a key factor of ATDH, while Hepatocyte nuclear factor 4α (HNF4α) and hepatocyte nuclear factor 4 alpha-antisense-1 (HNF4α-AS1) may have co-regulating relationship with PXR. This study aimed to explore whether the genetic variants of HNF4α and HNF4α-AS1 are associated with the predisposition of ATDH.
TB patients diagnosed in West China Hospital between December 2014 and April 2018 were enrolled. TagSNPs in HNF4α and HNF4α-AS1 gene from the samples of the patients were genotyped with a custom-designed 2×48-plex SNP ScanTM Kit. The frequencies of the alleles, genotypes, genetic models and haplotype distribution of the variants were compared between the case and control groups. The association between SNP and ATDH risk was assessed by single factor logistic regression.
Logistic regression analysis showed that none of the 15 genetic variants in HNF4α and HNF4α-AS1 genes were significantly associated with susceptibility to ATDH in the Chinese Han population after Bonferroni correction.
A challenge has arisen to the promising application of SNPs in the HNF4α and HNF4α-AS1 genes as genetic markers for ATDH, and further study is needed with a larger sample size.
世界卫生组织（WHO）推荐的结核病（TB）治疗药物最严重和常见的并发症是抗结核药物性肝毒性（ATDH）。孕烷 X 受体（PXR）是 ATDH 的关键因素，而肝细胞核因子 4α（HNF4α）和肝细胞核因子 4α-反义-1（HNF4α-AS1）可能与 PXR 具有共同调节关系。本研究旨在探讨 HNF4α 和 HNF4α-AS1 的遗传变异是否与 ATDH 的易感性有关。
纳入 2014 年 12 月至 2018 年 4 月在华西医院诊断为 TB 的患者。采用定制的 2×48-plex SNP ScanTM 试剂盒对患者样本中的 HNF4α 和 HNF4α-AS1 基因中的标签 SNP 进行基因分型。比较病例组和对照组中变异的等位基因、基因型、遗传模型和单倍型分布频率。采用单因素 logistic 回归评估 SNP 与 ATDH 风险的相关性。
经 Bonferroni 校正后，HNF4α 和 HNF4α-AS1 基因中的 15 个遗传变异均与中国汉族人群 ATDH 的易感性无显著相关性。
HNF4α 和 HNF4α-AS1 基因中的 SNP 作为 ATDH 的遗传标志物，其应用前景受到挑战，需要进一步扩大样本量进行研究。
