Heme Oxygenase-1 and Hemopexin Gene Polymorphisms and the Risk of Anti-Tuberculosis Drug-Induced Hepatotoxicity in China

Abstract

Objective: To assess whether the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) might be influenced by haem oxygenase-1 ( HMOX1) and haemopexin ( HPX) gene polymorphisms. Methods: A dynamic anti-tuberculosis treatment cohort was constructed, and the 1:4 matched nested case–control study was analysed. Eight single nucleotide polymorphisms (SNPs) of the two genes were selected for genotyping and Bonferroni correction was performed to correct for multiple comparison. Results: Overall, 7.8% of patients developed ATDH. SNP rs1807714 in the HMOX1 gene had decreased effects on the risk of moderate and severe hepatotoxicity under the dominant and additive models, and hepatocellular injury under the additive model. SNP rs2682099 in the HPX gene had increased effects on the risk of moderate and severe hepatotoxicity under the recessive model. However, these associations disappeared after Bonferroni correction. Conclusion: HMOX1 and HPX gene polymorphisms might not be associated with susceptibility to ATDH in the Chinese population.

Double-edged functions of hemopexin in hematological related diseases: from basic mechanisms to clinical application

“…Subjects exposed to heme challenges induced by heme infusions and phenylhydrazine survived (114). With the application of precision medicine and genome sequencing, the relationship between HPX genes and individualized drug side effects as well as tumorigenesis needs to be further investigated (115,116).…”

Hepatic Adverse Effects of Anti-Mycobacterium Tuberculosis Drugs and Their Associations with Various Genetic Variants

“…Results stated that the HMOX1 gene might not be related to the risk of developing ATDH. (Liu et al 2022) SLCO1B1 AND UGT1A1 Hepatocellular uptake of many compounds and drugs by organic anion transporter OATP1B is encoded by Solute carrier organic anion transporter family member 1B1(SCOL1B1 ) (Voora et al 2009). Vulnerability to ATDH has also been observed in the Chinese population when the prospective study was performed by using 34 tag SNPs in SLCO1B1 and UDP glucuronosyltransferase family 1 member A1 (sUGT1A1) on 466 patients.…”