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- Title
The role of the genetic variant FECH rs11660001 in the occurrence of anti‐tuberculosis drug‐induced liver injury.
- Authors
Zhang, Meiling; Zhu, Jia; Wang, Nannan; Liu, Wenpei; Lu, Lihuan; Pan, Hongqiu; He, Xiaomin; Yi, Honggang; Tang, Shaowen
- Abstract
What is known and objective: The pathogenic mechanism of anti‐tuberculosis drug‐induced liver injury (AT‐DILI) is still largely unknown. Recent studies have indicated that rifampicin and isoniazid cotreatment causes the accumulation of endogenous protoporphyrin IX in the liver through the haem biosynthesis pathway. Alanine synthase 1 (ALAS1) and ferrochelatase (FECH) are the rate‐limiting enzymes in the production of haem. The present study aimed to investigate the genetic contribution of the ALAS1 and FECH genes to the risk of AT‐DILI in an Eastern Chinese Han population. Methods: A 1:4 matched case–control study was conducted, and eight SNPs in the ALAS1 and FECH genes were detected and assessed. A multivariate conditional logistic regression model was used to estimate the association between genotypes and the risk of AT‐DILI by the odds ratios (ORs) with 95% confidence intervals (CIs), with liver disease history, hepatoprotectant use, smoking and drinking history as covariates. Results and discussion: Overall, 202 AT‐DILI cases and 808 controls were included in this study. The female patients carrying polymorphisms of rs11660001 in FECH had an increased risk of AT‐DILI under the dominant and additive models (OR = 1.831, 95% CI: 1.014–3.307, p = 0.045; OR = 1.673, 95% CI: 1.015–2.760, p = 0.044, respectively). The peak aspartate transaminase level was significantly higher in female patients carrying the GA+AA genotype of rs11660001 than in those with the GG genotype during anti‐TB treatment (p = 0.032). What is new and conclusion: Based on this 1:4 individual matched case–control study, SNP rs11660001 in the FECH gene may be associated with susceptibility to AT‐DILI in Chinese female anti‐TB treatment patients. Further studies in larger varied populations are needed to validate our findings.
- Subjects
CHINA; LIVER injuries; CONFIDENCE intervals; GENETIC polymorphisms; CASE-control method; LIVER diseases; ALANINE; SEX distribution; ANTITUBERCULAR agents; DESCRIPTIVE statistics; GENOTYPES; ALCOHOL drinking; POPULATION health; AMINO acids; LOGISTIC regression analysis; ODDS ratio; SMOKING; ASPARTATE aminotransferase
- Publication
Journal of Clinical Pharmacy & Therapeutics, 2022, Vol 47, Issue 8, p1276
- ISSN
0269-4727
- Publication type
Article
- DOI
10.1111/jcpt.13672