Polymorphism of <i>PXR</i>
 gene associated with the increased risk of drug-induced liver injury in Indonesian pulmonary tuberculosis patients

Zazuli, Zulfan; Barliana, Melisa Intan; Mulyani, Ully Adhie; Perwitasari, Dyah Aryani; Ng, Henry; Abdulah, Rizky

doi:10.1111/jcpt.12325

Cited by 24 publications

(33 citation statements)

References 35 publications

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“…A study that examined genotypes and haplotypes with six SNPs in the PXR gene in female Chinese populations found associations between PXR genetic polymorphisms (rs2461823 and rs7643645) and increased risk of AT-DILI [82]. Genotypes of another PXR polymorphism (rs3814055) were found to associate with a greater risk of AT-DILI in a study of 106 Indonesian patients [83]. SNPs rs2461823 and rs7643645 are located in the first intron of the PXR gene.…”

Section: Specific Molecular Mechanisms Of Isoniazid/rifampicin-inducementioning

confidence: 99%

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: 99%

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

Bao

Rasmussen

et al. 2018

Curr Pharmacol Rep

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“…Thirty-eight articles (29 distinct patient cohorts) investigated the association between GSTM1/GSTT1 or other genetic variants and anti-TB drug-related toxicity. In this review, we include data from 35 articles (22–56), which included 28 distinct patient cohorts. We did not include data from two articles (57, 58) as the data presented were unclear and we were unable to clarify the data with the authors.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-four articles provided a rationale for the choice of genes and SNPs to be investigated. Eleven articles (7, 22, 30, 43, 44, 46, 48, 50, 54–56) did not provide such information; however, none of these articles limited their reporting to only statistically significant associations. Consequently, there is no evidence to suggest that selective reporting of genes and SNPs is an issue of concern for the included studies.…”

Section: Resultsmentioning

confidence: 99%

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Association of variants within the GST and other genes with anti-tubercular agents related toxicity: a systematic review and meta-analysis

Richardson

Kirkham

Dwan

et al. 2019

Preprint

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Background Individuals receiving treatment with anti-tuberculosis (TB) drugs may experience serious side-effects, such as anti-TB drug-induced hepatotoxicity (ATDH). Genetic variants, such as polymorphisms of the GST gene and other genes, may increase the risk of experiencing such toxicity events. This systematic review and meta-analysis provides a comprehensive evaluation of the evidence base for associations between variants of the GST gene and other genes and toxicity outcomes related to anti-TB drugs. Methods We searched for relevant studies in MEDLINE, PubMed, EMBASE, BIOSIS and Web of Science. We pooled effect estimates for each genotype on each outcome, and stratified all analyses by country. We qualitatively assessed the methodological quality of the included studies. Results We included data from 28 distinct cohorts of patients in the review. The methodological quality of included studies was variable, with several important areas of concern. For GSTM1, patients with the homozygous null genotype were significantly more likely to experience hepatotoxicity than patients with heterozygous or homozygous present genotype (odds ratio [OR]=1.44, 95% confidence interval [CI] 1.15, 1.82). Moderate heterogeneity was observed in this analysis (I2=51.2%). No significant difference was observed for the GSTT1 null polymorphism. For the rs3814057 polymorphism of the PXR gene, both heterozygous genotype and homozygous mutant-type significantly increased hepatotoxicity risk compared with homozygous wild-type (heterozygous versus homozygous wild-type: OR=1.98, 95% CI 1.06, 3.69; I2=0%; homozygous mutant-type versus homozygous wild-type: OR=2.18, 95% CI 1.07, 4.44; I2=0%). Conclusions We found that it is challenging to perform robust synthesis of the evidence base for associations between GST and other genetic variants and toxicity related to anti-TB drugs. We identified significant associations between the GSTM1 null and PXR rs3814057 polymorphisms and ATDH. To the best of our knowledge, no meta-analyses on genetic variants other than variants of the NAT2, CYP2E1, GSTM1 and GSTT1 genes have been published. Our results therefore add to the existing understanding of the association between genetic variants and hepatotoxicity.

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“…In addition, Kurzawski M et al revealed that there were significant differences in tacrolimus concentrations between patients with different NR1I2 rs3814055: C > T genotypes (Kurzawski, Malinowski, Dziewanowski, & Drozdzik, 2017). And Zazuli et al (2015) found that, in Indonesian patients with tuberculosis, the TT genotype of rs3814055 had a significantly greater risk of antituberculosis drug-induced liver injury than those of CC genotype. The SNP rs1540339 is situated in the intron region of VDR.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of pharmacogenomic VIP variants in the Blang population from Yunnan Province of China

Zhang

Guo

Cheng

et al. 2019

Molec Gen & Gen Med

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Background Genetic polymorphisms in numerous pharmacogenetics studies were regarded as the essential factors involved in the response to or metabolism of drugs. These genetic variants called very important pharmacogenetic (VIP) variants played a role in drugs metabolism, which have been summarized in the PharmGKB database. In this study, we genotyped 80 VIP variants from the PharmGKB in 100 members of Blang volunteers from Yunnan province. Methods Based on the PharmGKB database, we genotyped 80 VIP variants loci located in 47 genes. We used χ 2 tests to evaluate the significant loci between Blang and the other populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. The global variation distribution of the significant variants was observed from the ALlele FREquency Database. And then, we used F ‐statistics (Fst), genetic structure, and phylogenetic tree analyses to ascertain the genetic affinity among 12 populations. Results Comparing the Blang with the other 11 populations from the HapMap Project, the statistical results revealed that rs3814055 (NC_000003.12:g.119781188C>T) of nuclear receptor subfamily 1 group I member 2 ( NR1I2 , OMIM# 603,065) was the most significant variant, followed by rs1540339 (NC_000012.12:g.47863543C>T) of vitamin D receptor ( VDR , OMIM#601,769). Furthermore, we found that genotype frequency of rs3814055 in the Blang was closer to the populations distributed in Miao. And genetic structure and F ‐statistics indicated that the Blangs had a relatively closer affinity with CHD, CHB, and JPT populations. In addition, the Han nationality in Shaanxi was closer to it. Conclusions Our results will complement the pharmacogenomics information of the Blang ethnic group and provide a theoretical basis for safer drug administration for Blang.

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Polymorphism of PXR gene associated with the increased risk of drug-induced liver injury in Indonesian pulmonary tuberculosis patients

Abstract: The result suggests that in Indonesian patients with tuberculosis, the risk of having AT-DILI was associated with TT genotype of the PXR gene.

Cited by 24 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 of variants within the GST and other genes with anti-tubercular agents related toxicity: a systematic review and meta-analysis

Genetic analysis of pharmacogenomic VIP variants in the Blang population from Yunnan Province of China

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