<i>NAT2</i> Genotypes in Moroccan Patients with Hepatotoxicity Due to Antituberculosis Drugs

Guaoua, Soukaina; Ratbi, Ilham; Bouazzi, Omaima El; Hammi, S.; Tebaa, Amina; Bourkadi, Jamal Eddine; Bencheikh, Rachida Soulaymani; Sefiani, Abdelaziz

doi:10.1089/gtmb.2016.0060

Cited by 13 publications

(8 citation statements)

References 22 publications

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“… were excluded due to overlap with their other studies (we therefore selected the later publication to analyse the distribution of the NAT2 genotype); three studies, by Guaoua et al . , Ng and Mishra et al . , were excluded as controls were not TB patients but healthy people; the studies by Roy et al .…”

Section: Resultsmentioning

confidence: 99%

The association between the NAT2 genetic polymorphisms and risk of DILI during anti‐TB treatment: a systematic review and meta‐analysis

Zhang

Wang

Wilffert

et al. 2018

Brit J Clinical Pharma

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AimsThe aim of this study is to evaluate the potential association between N‐acetyltransferase type 2 (NAT2) polymorphisms and drug‐induced liver injury during anti‐TB treatment (AT‐DILI).MethodsWe conducted a systematic review and performed a meta‐analysis to clarify the role of NAT2 polymorphism in AT‐DILI. PubMed, Medline and EMBASE databases were searched for studies published in English to December 31, 2017, on the association between the NAT2 polymorphism and AT‐DILI risk. Outcomes were pooled with random‐effects meta‐analysis. Details were registered in the PROSPERO register (number: CRD42016051722).ResultsThirty‐seven studies involving 1527 cases and 7184 controls were included in this meta‐analysis. The overall odds ratio (OR) of AT‐DILI associated with NAT2 slow acetylator phenotype was 3.15 (95% CI 2.58–3.84, I 2 = 51.3%, P = 0.000). The OR varied between different ethnic populations, ranging from 6.42 (95% CI 2.41–17.10, I 2 = 2.3%) for the West Asian population to 2.32 (95% CI 0.58–9.24, I 2 = 80.3%) for the European population. Within the slow NAT2 genotype, variation was also observed; NAT2*6/*7 was associated with the highest risk of AT‐DILI (OR = 1.68, 95% CI 1.09–2.59) compared to the other slow NAT2 acetylators combined.Conclusions NAT2 slow acetylation was observed to increase the risk of AT‐DILI in tuberculosis patients. Our results support the hypothesis that the slow NAT2 genotype is a risk factor for AT‐DILI.

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Section: Resultsmentioning

confidence: 99%

The association between the NAT2 genetic polymorphisms and risk of DILI during anti‐TB treatment: a systematic review and meta‐analysis

Zhang

Wang

Wilffert

et al. 2018

Brit J Clinical Pharma

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“…Additional clinical studies support the association between SA phenotypes and an increased risk of AT-DILI in Thai [49], Indonesian [50], and Singapore populations [51]. Another study conducted in Moroccan patients observed no NAT2 RA ( Nat2*4 ) alleles in the patients that developed AT-DILI [52]. Based on these findings, a model for predicting risk of AT-DILI based on NAT2 genotypes was established for Japanese patients [53].…”

Section: Specific Molecular Mechanisms Of Isoniazid/rifampicin-inducementioning

confidence: 92%

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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“…There are a continuously increasing number of identified sequences of polymorphisms related to the occurrence of antituberculosis drug-induced hepatotoxicity (ATDH): for example, genetic variants within N-acetyltransferase 2 (NAT2), nuclear receptor subfamily 1 group I member 2 (PXR), and solute carrier organic anion transporter family member 1B1 (SLCO1B1) genes. [13][14][15] Several published literatures have shown that lncRNAs are significantly associated with the drug effects and resistance in various malignant diseases. 16,17 For example, in the breast cancer cell experiment, researchers found that downregulation of lncRNA ROR inhibited the resistance to Tamoxifen.…”

Section: Found Aberrant Expressionmentioning

confidence: 99%

“…For antituberculosis drugs (ATDs), hepatotoxicity is known as the most serious and prevalent adverse drug reaction. There are a continuously increasing number of identified sequences of polymorphisms related to the occurrence of antituberculosis drug‐induced hepatotoxicity (ATDH): for example, genetic variants within N‐acetyltransferase 2 ( NAT2 ), nuclear receptor subfamily 1 group I member 2 ( PXR ), and solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ) genes . Several published literatures have shown that lncRNAs are significantly associated with the drug effects and resistance in various malignant diseases .…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms of long noncoding RNA RP11‐37B2.1 associate with susceptibility of tuberculosis and adverse events of antituberculosis drugs in west China

Song

Liu

Zhao

et al. 2019

Clinical Laboratory Analysis

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BackgroundLittle knowledge about the biological functions of RP11‐37B2.1, a newly defined long noncoding RNA (lncRNA) molecule, is currently available. Previous studies have shown rs160441, located in the RP11‐37B2.1 gene, is significantly associated with tuberculosis (TB) in a Ghanaian and the Gambian populations.MethodsWe investigated the influence of single‐nucleotide polymorphisms (SNPs) within lncRNA RP11‐37B2.1 on the risk of TB and the possible correlation with adverse drug reactions (ADRs) from TB treatment in a Western Chinese population. Four SNPs within lncRNA RP11‐37B2.1 were genotyped in 554 TB cases and 561 healthy subjects using the improved multiplex ligation detection reaction method, and the patients were followed up monthly to monitor the development of ADRs.ResultsNo significant association between the SNPs of lncRNA RP11‐37B2.1 and TB susceptibility was observed (all P > 0.05). Surprisingly, significant association was observed between two SNPs (rs218916 and rs160441) and thrombocytopenia development during anti‐TB therapy under the dominant model (P = 0.003 and 0.014, respectively).ConclusionsOur findings firstly exhibit that rs218916 and rs160441 within lncRNA RP11‐37B2.1 significantly associate with the occurrence of thrombocytopenia and suggest RP11‐37B2.1 genetic variants are potential biosignatures for thrombocytopenia during anti‐TB treatment.

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NAT2 Genotypes in Moroccan Patients with Hepatotoxicity Due to Antituberculosis Drugs

Abstract: There were no fast acetylator genotypes found among the patients having INH-hepatotoxicity. This finding suggests that the slow acetylator phenotype may contribute to the development of TB treatment hepatotoxicity.

Cited by 13 publications

References 22 publications

The association between the NAT2 genetic polymorphisms and risk of DILI during anti‐TB treatment: a systematic review and meta‐analysis

The association between the NAT2 genetic polymorphisms and risk of DILI during anti‐TB treatment: a systematic review and meta‐analysis

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

Genetic polymorphisms of long noncoding RNA RP11‐37B2.1 associate with susceptibility of tuberculosis and adverse events of antituberculosis drugs in west China

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