ArticleJournal of molecular biology2009
Functional study of the P32T ITPA variant associated with drug sensitivity in humans.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 58 citations in OpenAlex.
- Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C.World journal of gastroenterology · 2012Trial
- Inosine triphosphate pyrophosphatase from Trypanosoma brucei cleanses cytosolic pools from deaminated nucleotides.Scientific reports · 2022Article
- Article
- Measuring deaminated nucleotide surveillance enzyme ITPA activity with an ATP-releasing nucleotide chimera.Nucleic acids research · 2017Article
- The relationship between ITPA rs1127354 polymorphisms and efficacy of antiviral treatment in Northeast Chinese CHC patients.Medicine · 2017Observational
- Variant Inosine Triphosphatase Phenotypes Are Associated With Increased Ribavirin Triphosphate Levels.Journal of clinical pharmacology · 2017Article
- A disease spectrum for ITPA variation: advances in biochemical and clinical research.Journal of biomedical science · 2016Review
- Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells.Scientific reports · 2016Article
- The ITPA and C20orf194 Polymorphisms and Hematological Changes During Treatment With Pegylated-Interferon Plus Ribavirin in Patients With Chronic Hepatitis C.Hepatitis monthly · 2016Article
- Role of ITPA gene polymorphism in ribavirin-induced anemia and thrombocytopenia in Egyptian patients with chronic hepatitis C.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2016Article
- Role of genetic polymorphisms in hepatitis C virus chronic infection.World journal of clinical cases · 2015Article
- Association between IPTA gene polymorphisms and hematological abnormalities in hepatitis C virus-infected patients receiving combination therapy.Gut and liver · 2015Article
- Review article: genetic factors that modify the outcome of viral hepatitis.Alimentary pharmacology & therapeutics · 2014Review
- Individualization of chronic hepatitis C treatment according to the host characteristics.World journal of gastroenterology · 2014Review
- Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy.World journal of gastrointestinal pharmacology and therapeutics · 2013Article
- GLiMMPS: robust statistical model for regulatory variation of alternative splicing using RNA-seq data.Genome biology · 2013Article
- The human ITPA polymorphic variant P32T is destabilized by the unpacking of the hydrophobic core.Journal of structural biology · 2013Article
- Structural and functional characterization of a noncanonical nucleoside triphosphate pyrophosphatase from Thermotoga maritima.Acta crystallographica. Section D, Biological crystallography · 2013Article
- Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools.Environmental and molecular mutagenesis · 2012Review
- Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Sanitization of the cellular nucleotide pools from mutagenic base analogues is necessary for the accuracy of transcription and replication of genetic material and plays a substantial role in cancer prevention. The undesirable mutagenic, recombinogenic, and toxic incorporation of purine base analogues [i.e., ITP, dITP, XTP, dXTP, or 6-hydroxylaminopurine (HAP) deoxynucleoside triphosphate] into nucleic acids is prevented by inosine triphosphate pyrophosphatase (ITPA). The ITPA gene is a highly conserved, moderately expressed gene. Defects in ITPA orthologs in model organisms cause severe sensitivity to HAP and chromosome fragmentation. A human polymorphic allele, 94C-->A, encodes for the enzyme with a P32T amino acid change and leads to accumulation of non-hydrolyzed ITP. ITPase activity is not detected in erythrocytes of these patients. The P32T polymorphism has also been associated with adverse sensitivity to purine base analogue drugs. We have found that the ITPA-P32T mutant is a dimer in solution, as is wild-type ITPA, and has normal ITPA activity in vitro, but the melting point of ITPA-P32T is 5 degrees C lower than that of wild-type. ITPA-P32T is also fully functional in vivo in model organisms as determined by a HAP mutagenesis assay and its complementation of a bacterial ITPA defect. The amount of ITPA protein detected by Western blot is severely diminished in a human fibroblast cell line with the 94C-->A change. We propose that the P32T mutation exerts its effect in certain human tissues by cumulative effects of destabilization of transcripts, protein stability, and availability.
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Registered trials
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.