Update meta-analysis of theCYP2E1 RsaI/PstI andDraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies

Wang, F.-J.; Wang, Y.; Niu, Ting; Lu, Wusheng; Sandford, Andrew J.; He, Jian‐Qing

doi:10.1111/jcpt.12388

Cited by 19 publications

(31 citation statements)

References 35 publications

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“…The studies included in the meta-analysis examined Chinese, Korean, and Japanese populations. Recently, an updated meta-analysis assessed a larger set of data from 26 studies with a total of 7423 participants [58]. The results confirmed an increased risk of the CYP2E1 C1/C1 genotype for occurrence of AT-DILI.…”

Section: Specific Molecular Mechanisms Of Isoniazid/rifampicin-inducementioning

confidence: 84%

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Bao

Rasmussen

et al. 2018

Curr Pharmacol Rep

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Purpose of this Review In order to combat the development of drug resistance, the clinical treatment of tuberculosis requires the combined use of several anti-tuberculosis (anti-TB) drugs, including isoniazid and rifampicin. Combinational treatment approaches are suggested by the World Health Organization (WHO) and are widely accepted throughout the world. Unfortunately, a major side effect of the treatment is the development of anti-tuberculosis drug-induced liver injury (AT-DILI). Many factors contribute to isoniazid- and rifampicin-mediated AT-DILI and genetic variations are among the most common factors. The purpose of this review is to provide information on genetic variations associated with isoniazid- and rifampicin-mediated AT-DILI. Recent Findings The genetic variations associated with AT-DILI have been identified in the genomic regions within or near genes encoding proteins in the following pathways: drug metabolizing enzymes (NAT2, CYP2E1, and GSTs), accumulation of bile acids, lipids, and heme metabolites (CYP7A1, BSEP, UGTs, and PXR), immune adaptation (HLAs and TNF-α), and oxidant challenge (TXNRD1, SOD1, BACH1, and MAFK). Summary The information summarized in this review considers the genetic bases of risk factors contributing to AT-DILI and provides information that may help for future studies. Some of the implicated genetic variations can be used in the design of genetic tests and serve as biomarkers for the prediction of isoniazid- and rifampicin-mediated AT-DILI risk in personalized medicine.

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Section: Specific Molecular Mechanisms Of Isoniazid/rifampicin-inducementioning

confidence: 84%

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Bao

Rasmussen

et al. 2018

Curr Pharmacol Rep

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“…In CYP2E1 , two polymorphisms are most commonly studied ( RsaI/PstI (rs2031920/rs3813867) and DraI (rs6413432)). rs2031920 and rs3813867 are in complete linkage disequilibrium in East Asians [ 16 ]. A recent meta-analysis found that the RsaI/PstI polymorphism c1/c1 (major allele for both SNPs) confers a higher risk of INH-DILI with an OR of 1.32 compared to the c1/c2 or c2/c2 genotypes, but no increase in risk for the DraI polymorphism [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients

et al. 2017

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Background and aimsIsoniazid (INH) is part of the first-line-therapy for tuberculosis (TB) but can cause drug-induced liver injury (DILI). Several candidate single nucleotide polymorphisms (SNPs) have been previously identified but the clinical utility of these SNPs in the prediction of INH-DILI remains uncertain. The aim of this study was to assess the association between selected candidate SNPs and the risk of INH-DILI and to assess the clinical validity of associated variants in a Singaporean population.MethodsThis was a case-control study where 24 INH-DILI cases and 79 controls were recruited from the TB control unit in a tertiary hospital. Logistic regression was used to test for the association between candidate SNPs and INH-DILI. NAT2 acetylator status was inferred from genotypes and tested for association with INH-DILI. Finally, clinical validity measures were estimated for significant variants.ResultsTwo SNPs in NAT2 (rs1041983 and rs1495741) and NAT2 slow acetylators (SA) were significantly associated with INH-DILI (OR (95% CI) = 13.86 (4.30–44.70), 0.10 (0.03–0.33) and 9.98 (3.32–33.80), respectively). Based on an INH-DILI prevalence of 10%, the sensitivity, specificity, positive and negative predictive values of NAT2 SA were 75%, 78%, 28% and 97%, respectively. The population attributable fraction (PAF) and number needed to test (NNT) for NAT2 SA were estimated to be 0.67 and 4.08, respectively. A model with clinical and NAT2 acetylator status provided significantly better prediction for INH-DILI than a clinical model alone (area under receiver operating characteristic curve = 0.863 vs. 0.766, respectively, p = 0.027).ConclusionsWe show the association between NAT2 SA and INH-DILI in a Singaporean population and demonstrated its clinical utility in the prediction of INH-DILI.

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“…Polymorphic variants, existing in the functional genes of the cytochrome P450 system, are associated with the pathogenesis of several clinical cancers [ 2 , 3 ]. For example, rs2031920 C/T with an Rsa I restriction enzyme site and rs3813867 C/T with a Pst I restriction enzyme site are two common single nucleotide polymorphisms (SNP) within the 5′-flanking regions of the CYP2E1 gene [ 4 – 6 ]. Three genotypes of c1/c1, c1/c2, c2/c2 were generated; rs2031920 and rs3813867 were in close linkage disequilibrium [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…For example, rs2031920 C/T with an Rsa I restriction enzyme site and rs3813867 C/T with a Pst I restriction enzyme site are two common single nucleotide polymorphisms (SNP) within the 5′-flanking regions of the CYP2E1 gene [ 4 – 6 ]. Three genotypes of c1/c1, c1/c2, c2/c2 were generated; rs2031920 and rs3813867 were in close linkage disequilibrium [ 4 – 6 ]. Furthermore, CYP2E1 polymorphisms were reported to be linked to several cancers, such as nasopharyngeal carcinoma [ 7 ], urinary cancers [ 6 ] and head and neck carcinoma [ 5 ], particularly in Asian populations.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the role of rs2031920 and rs3813867 polymorphisms within the cytochrome P450 2E1 gene in the risk of squamous cell carcinoma

Hai

2018

Cancer Cell Int

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BackgroundTo explore the genetic effect of rs2031920 and rs3813867 polymorphisms within the cytochrome P450 2E1 (CYP2E1) gene on the risk of squamous cell carcinoma (SCC), a meta-analysis was performed.MethodsThe eligible case–control studies were obtained by database searching and screening, and the specific statistical analysis was performed with STATA 12.0 software.ResultsAfter the process of database searching and screening, a total of 32 case–control studies with 7435 cases and 10,466 controls were ultimately included in our meta-analysis. With regard to the rs2031920 C/T polymorphism, in comparison to controls, a reduced risk in cases of esophageal squamous cell carcinoma (ESCC) was detected for the models of allele T vs. allele C [P = 0.025, odds ratio (OR) = 0.67], carrier T vs. carrier C (P = 0.014, OR = 0.70), TT vs. CC (P = 0.029, OR = 0.65), CT vs. CC (P = 0.040, OR = 0.56), CT + TT vs. CC (P = 0.035, OR = 0.58). Similarly, a decreased SCC risk was observed for the rs3813867 G/C polymorphism in the allele, carrier, homozygote, dominant, and recessive models of overall SCC meta-analysis and “ESCC” subgroup analysis (all P < 0.05, OR < 1) and in all genetic models of “Asian” and “population-based control (PB)” subgroup analysis (all P < 0.05, OR < 1). Additionally, for the rs2031920/rs3813867 haplotype, a decreased SCC risk was also detected in the overall SCC meta-analysis under the allele, carrier, homozygote and dominant model (all P < 0.05, OR < 1) and the subgroup analysis of “PB” under the allele, carrier, and dominant models (all P < 0.05, OR < 1).ConclusionsOur meta-analysis supports the “T” allele carrier of the CYP2E1 rs2031920 C/T polymorphism and “C” allele carrier of the rs3813867 G/C polymorphism as protective factors for ESCC patients, especially in Asian populations.

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Update meta-analysis of theCYP2E1 RsaI/PstI andDraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies

Abstract: This meta-analysis suggests that there is an increased risk of ATDH in individuals carrying the C1/C1 genotype of the CYP2E1 RsaI/PstI polymorphism. However, no association was found for the DraI polymorphism.

Cited by 19 publications

References 35 publications

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Genetic Variations Associated with Anti-Tuberculosis Drug-Induced Liver Injury

Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients

Analysis of the role of rs2031920 and rs3813867 polymorphisms within the cytochrome P450 2E1 gene in the risk of squamous cell carcinoma

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