ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
A GAG trinucleotide-repeat polymorphism in the gene for glutathione biosynthetic enzyme, GCLC, affects gene expression through translation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Randomized controlled trial of oral glutathione supplementation on body stores of glutathione.European journal of nutrition · 2015Trial
- Plasma advanced oxidative protein products are associated with anti-oxidative stress pathway genes and malaria in a longitudinal cohort.Malaria journal · 2014Trial
- Polymorphisms of theLife (Basel, Switzerland) · 2023Article
- Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis.Biomedicines · 2022Article
- Role of glutathione biosynthesis in endothelial dysfunction and fibrosis.Redox biology · 2018Article
- Association of GCLM -588C/T and GCLC -129T/C Promoter Polymorphisms of Genes Coding the Subunits of Glutamate Cysteine Ligase with Ischemic Heart Disease Development in Kazakhstan Population.Disease markers · 2017Article
- Genetic Polymorphism Associated Prefrontal Glutathione and Its Coupling With Brain Glutamate and Peripheral Redox Status in Early Psychosis.Schizophrenia bulletin · 2016Article
- Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).International journal of molecular medicine · 2015Review
- Significance of Polymorphisms and Expression of Enzyme-Encoding Genes Related to Glutathione in Hematopoietic Cancers and Solid Tumors.BioMed research international · 2015Review
- A functional trinucleotide repeat polymorphism in the 5'-untranslated region of the glutathione biosynthetic gene GCLC is associated with increased risk for lung and aerodigestive tract cancers.Molecular carcinogenesis · 2013Article
- Glutathione defense mechanism in liver injury: insights from animal models.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2013Review
- Polymorphism in glutamate cysteine ligase catalytic subunit (GCLC) is associated with sulfamethoxazole-induced hypersensitivity in HIV/AIDS patients.BMC medical genomics · 2012Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
A guanine-adenine-guanine (GAG) repeat polymorphism with 5 different alleles (4, 7, 8, 9, and 10 repeats) in the 5' untranslated region (UTR) of GCLC has been associated with altered GCL activity and glutathione (GSH) levels. We investigated whether this polymorphism affects either transcription or translation using luciferase reporter constructs containing variant GCLC 5' UTRs. Higher luciferase activity was observed in HepG2 and human embryonic kidney 293 (HEK293) cells transfected with constructs containing either 8 or 9 repeats than in constructs containing 4, 7, or 10 repeats (P<0.05). In cell-free lysates, GAG repeat number had no effect on luciferase mRNA yield. In vitro translation of mRNAs from luciferase constructs resulted in differences similar to those found in cell cultures (P<0.05). A similar association of GAG repeat with GCLC phenotype was observed in vivo in healthy adults, as individuals with GAG-7/7 genotype had lower GCL activity and GSH levels in lymphocytes compared to those with GAG-9/9 (P<0.05). Higher GCL activity and GSH levels observed in red blood cells (RBCs) from individuals with GAG-7/7 compared to GAG-9/9 are likely due to differences in GCL regulation in RBCs. Altogether, these results suggest that GAG polymorphism affects GCLC expression via translation, and thus may be associated with altered risk for GSH-related diseases and toxicities.
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Registered trials
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