Antioxidant status and GST gene polymorphisms in antitubercular treatment-induced hepatotoxicity patients

Rana, Satya Vati; Kamboj, JK; Sharma, Sadhna; Ola, R. P.; Sinha, Saroj Kant; Singh, Kartar

doi:10.1007/s12072-013-9452-1

Cited by 6 publications

(7 citation statements)

References 28 publications

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“…All included articles were observational case‐control studies that investigated GSTs polymorphisms in TB patients with or without ATLI, of which eighteen were conducted in East Asians, eight in Indians, and three in Caucasians and Brazilians, respectively. Most studies used INH, RMP, PZA and EMB for TB treatment, with at least alanine aminotransferase (ALT)/aspartate aminotransferase (AST) more than twice the upper limit of normal (>2 ULN) as the main diagnostic criteria for liver injury.…”

Section: Resultsmentioning

confidence: 99%

Are genetic variations in glutathione S‐transferases involved in anti‐tuberculosis drug‐induced liver injury? A meta‐analysis

Zhang

2019

J Clin Pharm Ther

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What is known and Objective As a crucial protective role in the detoxifying mechanisms of drugs, glutathione S‐transferases (GSTs) may affect an individual patient's susceptibility to anti‐tuberculosis drug‐induced liver injury (ATLI). However, the results of studies investigate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and risk of ATLI are inconclusive. A meta‐analysis on this topic was performed. Methods PubMed, EMBASE, ISI web of science and the Chinese National Knowledge Infrastructure (CNKI) were systematically searched to identify relevant studies. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Heterogeneity among articles and publication bias were also tested. Results and discussion After excluding one study as an outlier, the null GSTM1 genotype was associated with an increased risk of ATLI (OR = 1.270, 95% CI (1.014‐1.590, P = .038), especially in East Asians (OR = 1.501, 95% CI (1.303‐1.730). With similar exclusion, the null GSTT1 genotype increased the risk of ATLI in the total population (OR = 1.169, 95% CI: 1.028‐1.330) and in Indians (OR = 1.732, 95% CI: 1.229‐2.416). No statistically significant association was observed between the mutant GSTP1 genotype with risk of ATLI, which may need more rigorous and uniform case‐control or cohort studies for more robust inferences. What is new and conclusion This up‐to‐date meta‐analysis strongly suggests associations of GSTM1 and GSTT1 polymorphisms with ATLI. The results show the increased risk of ATL1 with the null GSTM1 and GSTT1 genotype on ATLI development. No such association is shown with the mutant GSTP1 genotype.

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Section: Resultsmentioning

confidence: 99%

Are genetic variations in glutathione S‐transferases involved in anti‐tuberculosis drug‐induced liver injury? A meta‐analysis

Zhang

2019

J Clin Pharm Ther

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“…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. We did not include data from a third article (59) because for the GSTM1/GSTT1 gene, we suspected that data were reported for the same cohort of patients as that included in a more recent article by the same author (43). Data on other genetic variants presented in this third excluded article were unclear and we were unable to clarify the data with the authors.…”

Section: Resultsmentioning

confidence: 99%

“…If multiple articles report data for the same patient cohort, data for this patient cohort must only be included in meta-analysis once, otherwise participants are “double-counted”, and the pooled effect will be overly biased toward these outcome data, and the assumption about independence between cohorts will also be violated. For two articles (43, 59), we contacted study authors for clarification about patient cohort overlap but did not receive a response. Therefore, data from the older article (59) were excluded from meta-analyses to which both articles contributed data.…”

Section: Discussionmentioning

confidence: 99%

“…For two articles (43, 59), we contacted study authors for clarification about patient cohort overlap but did not receive a response. Therefore, data from the older article (59) were excluded from meta-analyses to which both articles contributed data. If the two articles reported data for distinct patient cohorts, then data has been lost by excluding one article.…”

Section: Discussionmentioning

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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“…The enzymatic activity of the proteins coded by the sequences of GSTM1 [73] and GSTP [74, 75] genes has been previously identified as a risk factor in diseases of oxidative stress and is associated with the risk of developing chronic severe ethanol liver damage. On the other side, CYP2D6 is a molecule of the cytochrome P450 superfamily that metabolizes several drugs and endogenous molecules.…”

Section: Discussionmentioning

confidence: 99%

Liver-Metabolizing Genes and Their Relationship to the Performance of Elite Spanish Male Endurance Athletes; a Prospective Transversal Study

2019

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BackgroundThe genetic profile that is needed to define an endurance athlete has been studied during recent years. The main objective of this work is to approach for the first time the study of genetic variants in liver-metabolizing genes and their role in endurance performance by comparing the allelic and genotypic frequencies in elite endurance athletes to the non-athlete population.MethodsGenotypic and allelic frequencies were determined in 123 elite endurance athletes (75 professional road cyclists and 48 endurance elite runners) and 122 male non-athlete subjects (sedentary). Genotyping of cytochrome P450 family 2 subfamily D member 6 (CYP2D6 rs3892097), glutathione-S transferase mu isoform 1 (GSTM1), glutathione S-transferase pi (GSTP rs1695) and glutathione S-transferase theta (GSTT) genes was performed by polymerase chain reaction (PCR). The combination of the polymorphisms for the “optimal” polygenic profile has been quantified using the genotype score (GS).ResultsStatistical differences were found in the genetic distributions between elite endurance athletes and non-athletes in CYP2D6 (p < 0.001) and GSTT (p = 0.014) genes. The binary logistic regression model showed a favourable OR (odds ratio) of being an elite endurance runner against a professional road cyclist (OR: 2.403, 95% CI: 1.213–4.760 (p = 0.002)) in the polymorphisms studied.ConclusionsGenotypic distribution of liver-metabolizing genes in elite endurance athletes is different to non-athlete subjects, with a favourable gene profile in elite endurance athletes in terms of detoxification capacity.

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Antioxidant status and GST gene polymorphisms in antitubercular treatment-induced hepatotoxicity patients

Cited by 6 publications

References 28 publications

Are genetic variations in glutathione S‐transferases involved in anti‐tuberculosis drug‐induced liver injury? A meta‐analysis

Are genetic variations in glutathione S‐transferases involved in anti‐tuberculosis drug‐induced liver injury? A meta‐analysis

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

Liver-Metabolizing Genes and Their Relationship to the Performance of Elite Spanish Male Endurance Athletes; a Prospective Transversal Study

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