Association of ABCC Gene Polymorphism With Susceptibility to Antituberculosis Drug-Induced Hepatotoxicity in Western Han Patients With Tuberculosis.
Hao BaiTao WuLin JiaoQian WuZhenzhen ZhaoJiajia SongTangyuheng LiuYanghua LvXiaojun LuBinwu YingPublished in: Journal of clinical pharmacology (2019)
Six-month combination regimens could lead to serious hepatotoxicity, which may limit the clinical use of antituberculosis drugs. ABCC transporters are critical to the influx and efflux of compounds into and out of cells. The aim of this study was to explore whether the genetic variants in ABCC genes were related to the development of antituberculosis drug-induced hepatotoxicity. Here, we screened and genotyped 39 single-nucleotide polymorphisms of 13 ABCC genes in 746 eligible patients treated by first-line antituberculosis drugs in Western China Hospital. Genomic DNA was extracted from a peripheral blood sample of each patient, and clinical symptoms and laboratory results were recorded regularly. We found that the incidence rate of hepatotoxicity was 15.8% in the western Chinese Han population. As a result, the ABCC2 rs3740065 genotype, sex, and the baseline level of alanine aminotransferase are independent risk factors of antituberculosis drug-induced hepatotoxicity, with P values of .008, .014, and <.001, respectively. Our findings revealed a fraction of the underlying mechanism of hepatotoxicity, and larger validation studies on different populations are warranted to confirm these findings.
Keyphrases
- drug induced
- liver injury
- risk factors
- adverse drug
- peripheral blood
- south africa
- induced apoptosis
- healthcare
- mycobacterium tuberculosis
- emergency department
- cell proliferation
- oxidative stress
- cell death
- circulating tumor
- depressive symptoms
- copy number
- single cell
- dna methylation
- signaling pathway
- physical activity
- hiv aids
- endoplasmic reticulum stress
- transcription factor
- sleep quality
- genome wide analysis
- hepatitis c virus