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The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury.

ABSTRACT: Background:TGFBRAP1 and TGFBR2 play important roles in the TGF-?/smad signalling pathway and may disturb liver homeostasis by regulating liver injury and renewal. However, little is known about the association between their genetic polymorphisms and antituberculosis drug-induced liver injury (ATDILI), so we explored the association between their variants and the susceptibility to ATDILI. Materials and Methods:A total of 746 tuberculosis patients were prospectively enrolled, and fifteen selected SNPs were genotyped. The allele, genotype, and genetic model frequencies of the variants were compared between patients with or without ATDILI, as well as the joint effect analysis of SNP-SNP interactions. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated. Results:The A variant at rs17687727 was significantly associated with an increased risk for ATDILI (OR 1.55; 95% CI: 1.08-2.22; p = 0.016), which is consistent with the results in the additive and dominant models. Other allele, genotype, and genetic model frequencies were similar in the two groups for the other fourteen SNPs (all p > 0.05). Conclusion:Our study first implied that the A variant of rs17687727 in TGFBRAP1 influenced the susceptibility to ATDILI in first-line antituberculosis combination treatment in the Han Chinese population in a dependent manner.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6724436 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury.

Zhang Jingwei J Zhao Zhenzhen Z Bai Hao H Jiao Lin L Wu Qian Q Wu Tao T Liu Tangyuheng T Hu Xuejiao X Song Jiajia J Lyv Mengyuan M Ying Binwu B

Evidence-based complementary and alternative medicine : eCAM 20190822

<h4>Background</h4>TGFBRAP1 and TGFBR2 play important roles in the TGF-<i>β</i>/smad signalling pathway and may disturb liver homeostasis by regulating liver injury and renewal. However, little is known about the association between their genetic polymorphisms and antituberculosis drug-induced liver injury (ATDILI), so we explored the association between their variants and the susceptibility to ATDILI.<h4>Materials and methods</h4>A total of 746 tuberculosis patients were prospectively enrolled, ...[more]

PMID: 31534460

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Project description:Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed, and the protocol was registered in PROSPERO (CRD42020200077). Five electronic databases were searched to identify eligible studies published between 1990 and 2022. Search terms included anti-TB treatment and drug-induced liver injury. Studies that reported the incidence of ATLI or provided sufficient data to calculate the incidence of ATLI were included, and duplicate studies were excluded. Meta-analysis was conducted on the basis of logit-transformed metrics for the incidence of ATLI with 95% confidence intervals (CIs), followed by a predefined subgroup meta-analysis. Temporal trend analyses were performed to describe the change in pooled incidence over time. A random effects metaregression was conducted to explore the source of heterogeneity. All statistical analyses were carried out using R 4.0.1. Results A total of 160 studies from 156 records with 116147 patients were included in the meta-analysis. Based on the random effects model, the pooled incidence of ATLI was 11.50% (95% CI: 10.10%–12.97%) and showed an upward trend over time (P < 0.001). Patients who received first-line anti-TB drugs, patients in South America, and patients with hepatitis B and C virus coinfection had a higher incidence of ATLI (13.66%, 18.16%, and 39.19%, respectively). Sensitivity analyses also confirmed this robust incidence after the exclusion of some studies. The metaregression showed that different anti-TB regimens and geographical regions were important explanatory factors of the heterogeneity between studies. Conclusions The present systematic review provided a basis for estimating the incidence of ATLI worldwide, which varied among patients with different anti-TB regimens in different geographical regions and with different coinfections and had an upward trend. Regular liver function monitoring is imperative for patient safety during the anti-TB treatment course.

Dataset Information

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury.

Publications

The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury.

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