Identification of single nucleotide polymorphisms in the human gamma-glutamyl hydrolase gene and characterization of promoter polymorphisms.

@article{Chave2003IdentificationOS,
  title={Identification of single nucleotide polymorphisms in the human gamma-glutamyl hydrolase gene and characterization of promoter polymorphisms.},
  author={Karen J. Chave and Thomas J. Ryan and Stacey E Chmura and John Galivan},
  journal={Gene},
  year={2003},
  volume={319},
  pages={
          167-75
        }
}
gamma-Glutamyl hydrolase (GGH) plays a central role in folate metabolism and antifolate action. Increased GGH activity has been found in rat hepatoma cells resistant to the cancer drug methotrexate (MTX). The aim of this study was to identify polymorphisms in the GGH gene that modulate GGH activity and that may affect methotrexate resistance. Exons of the human gamma-glutamyl hydrolase (hGGH) gene were amplified by polymerase chain reaction (PCR) from breast cancer tissue and leukemia cell… Expand
A substrate specific functional polymorphism of human gamma-glutamyl hydrolase alters catalytic activity and methotrexate polyglutamate accumulation in acute lymphoblastic leukaemia cells.
TLDR
A substrate specific functional SNP (452C>T) in the human GGH gene that is associated with lower catalytic activity and higher accumulation of long-chain MTX-PG in leukaemia cells of patients treated with HDMTX is demonstrated. Expand
Association between polymorphisms of dihydrofolate reductase and gamma glutamyl hydrolase genes and toxicity of high dose methotrexate in children with acute lymphoblastic leukemia.
TLDR
The GGH -401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy. Expand
Genotyping of single nucleotide polymorphism in γ‐glutamyl hydrolase gene by capillary electrophoresis
TLDR
The SSCP‐CE method was found to be feasible for SNP screening in the GGH gene and applied to detect genotyping of acute lymphoblastic leukemia patients receiving MTX treatment. Expand
The effect of polymorphisms of gamma-glutamyl hydrolase (GGH) gene on methotrexate-induced toxicity in acute lymphoblastic leukemia
TLDR
Evaluation of patients for methotrexate-related polymorphism of GGH gene may be useful to determine the appropriate dose of metotrexate and reducing its toxic side effects, and suggested that the T allele had a supporting role in prevention of thrombocytopenia. Expand
Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients.
TLDR
Frequency of two SNPs in FPGS and GGH genes and their associated with response to MTX in rheumatoid arthritis patients treated with MTX monotherapy are suggested not to be clinically important for MTX treatment outcome. Expand
Genetic Polymorphism of C452T (T127I) in Humanγ-Glutamyl Hydrolase in a Japanese Population(Biopharmacy)
TLDR
The C452T polymorphism of GGH was determined in 269 Japanese healthy volunteers by using polymerase chain reaction‐restriction fragment length polymorphism (PCR-RFLP) assay and it was found that twenty-nine out of 269 individuals had variant T allele, that the genotype distribution and allele frequency was similar to African‐Americans but significantly different from Caucasians. Expand
Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia
TLDR
FPGS rs1544105, GGH rs3758149, and MTHFR rs1801133 polymorphisms contribute to the variability of MTX pharmacokinetics, and their genotyping may be useful to reduce toxicities associated with MTX therapy. Expand
Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis.
TLDR
It is demonstrated that polymorphisms in SLC19A1 and GGH affect polyglutamation of MTX, and predicted independently and significantly MTXPG3-5 levels are significantly higher than the group median. Expand
Polymorphisms of the gamma-glutamyl hydrolase gene and risk of relapse to acute lymphoblastic leukemia in Mexico.
TLDR
The investigation suggests that the -401C/T polymorphism in the gamma-glutamyl hydrolase may be a factor involved in the generation of relapse to disease in patients with ALL. Expand
Interethnic differences in single and haplotype structures of folylpolyglutamate synthase and gamma-glutamyl hydrolase variants and their influence on disease susceptibility to acute lymphoblastic leukemia in the Indian population: An exploratory study
TLDR
FPGS rs1544105'AA' genotype was found to influence the risk for ALL and the impact of each variant on the susceptibility and outcome of diseases may differ between populations. Expand
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References

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TLDR
The complete organization and structure of the human GH gene was determined and studies of cDNA from different human tissue sources provided evidence that there is a single spliced cDNA species in human. Expand
Characterization of the human γ-glutamyl hydrolase promoter and its gene expression in human tissues and cancer cell lines
TLDR
The levels of hGH gene expression are high in tissues such as liver, kidney, and placenta as determined by Northern blot and RT-PCR analyses, and hGH expression is relatively low in spleen, lung, small intestine, and peripheral blood leukocytes; there was no significant difference in hGH mRNA levels between breast cancer tissues and their normal counterparts. Expand
Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro.
TLDR
A cDNA encoding human gamma-glutamyl hydrolase has been identified by searching an expressed sequence tag data base and using rat Gamma-glUTamyl Hydrolase cDNA as the query sequence, showing 67% identity to that of rat gamma- glutamy hydrol enzyme. Expand
Increased activity of gamma-glutamyl hydrolase in human sarcoma cell lines: a novel mechanism of intrinsic resistance to methotrexate (MTX).
TLDR
GGH activity was measured and found increased levels of this enzyme in MTX resistant soft tissue sarcoma cell lines and no appreciable difference of FPGS activity was observed between MTX-resistant and sensitive cells. Expand
gamma-Glutamyl hydrolase and folylpolyglutamate synthetase activities predict polyglutamylation of methotrexate in acute leukemias.
TLDR
Data suggest that the evaluation of both these enzymes at diagnosis may be used as a predictor of MTX polyglutamylation and therefore for response to MTX therapy and outcome. Expand
Site-directed mutagenesis establishes cysteine-110 as essential for enzyme activity in human gamma-glutamyl hydrolase.
TLDR
Results indicate that Cys-110 is essential for enzyme activity and suggest that GH is a cysteine peptidase, the first identification of the essential Cys residue in this enzyme. Expand
Characterization of human cellular gamma-glutamyl hydrolase.
TLDR
Results indicate that the identified cDNA encodes the intracellular gamma-glutamyl hydrolase found in a variety of human tumor cells and that the baculovirus-expressed enzyme is a suitable model for further structural and enzymatic studies. Expand
Cloning of mouse gamma-glutamyl hydrolase in the form of two cDNA variants with different 5' ends and encoding alternate leader peptide sequences.
TLDR
Cl cloning of this mouse lysosomal cDNA enzyme from liver GH mRNA in the form of two cDNA variants differing 14-fold (Variant I versus Variant II) in relative frequency that exhibited 5'-end heterogeneity and encoded alternate leader peptides is described. Expand
Glutamyl hydrolase. pharmacological role and enzymatic characterization.
TLDR
GH is being evaluated as an intracellular target for inhibition in order to enhance the therapeutic activity of antifolates and fluorouracil and suggests that Cys110 is the nucleophile that attacks the gamma-amide linkage and causes hydrolysis. Expand
Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia.
TLDR
Comparable lineage differences in normal lymphoid versus nonlymphoid cells suggest a lineage-specific control of FPGS expression, which could explain the superior outcome in children with B-lineage ALL treated with antimetabolite therapy. Expand
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