Influence of HNF4α and HNF4α-AS1 gene variants on the risk of anti-tuberculosis drugs-induced hepatotoxicity.

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.