ArticlePharmacogenetics and genomics2015
The influence of human GSTZ1 gene haplotype variations on GSTZ1 expression.
Article in Pharmacogenetics and genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Phase III trial of sodium dichloroacetate for pyruvate dehydrogenase complex deficiency in children.JCI insight · 2026Trial
- Trial
- Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases.International journal of nanomedicine · 2023Review
- Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity.Schizophrenia bulletin · 2020Article
- Age-Related Changes in miRNA Expression Influence GSTZ1 and Other Drug Metabolizing Enzymes.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Age-Related Changes in Expression and Activity of Human Hepatic Mitochondrial Glutathione Transferase Zeta1.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- GlutathioneDrug design, development and therapy · 2018Review
- Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.Pharmacology & therapeutics · 2017Review
- GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate.Biochimica et biophysica acta · 2016Article
- Pharmacogenetic considerations with dichloroacetate dosing.Pharmacogenomics · 2016Review
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND/
objectivesThe zeta-1 family isoform of GST biotransforms the investigational drug dichloroacetate (DCA) and certain other halogenated carboxylic acids. Haplotype variability in GSTZ1 influences the kinetics and, possibly, the toxicity of DCA. DCA metabolism correlates with expression of the GSTZ1 protein, so it is important to document variables that affect expression. Following up on a limited previous study, we tested the hypothesis that a coding single nucleotide polymorphism (SNP), the lysine (K) amino acid (E32>K) in GSTZ1 haplotypes linked to a promoter region SNP results in lower hepatic expression of GSTZ1. MATERIALS AND
methodsThe influence of K carrier and non-K carrier haplotypes on GSTZ1 expression was determined by analyzing 78 liver samples from individuals aged 7-84 years of various racial and ethnic backgrounds. GSTZ1 expression data were analyzed on the basis of the presence or absence of lysine 32.
resultsGSTZ1 protein expression differed significantly between K carrier and non-K carrier haplotypes (P=0.001) in Whites, but not in African-Americans (P=0.277). We attribute this difference in GSTZ1 expression among K carrier haplotypes in Whites to the linkage disequilibrium between the K or A allele from the G>A SNP (rs7975), within the promoter G>A-1002 SNP (rs7160195) A allele. There is no linkage disequilibrium between these two polymorphisms in African-Americans.
conclusionWe conclude that the lower expression of GSTZ1 in Whites who possess the K carrier haplotype results in lower enzymatic activity and slower metabolism of DCA, compared with those who possess the non-K carrier haplotype. These results further define safe, genetics-based dosing regimens for chronic DCA administration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.