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TPMT encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct.
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With the significant mitigation of TPMT wild type-expressing cells to cisplatin cytotoxicity, findings demonstrate a drug-gene interaction between increased TPMT activity and decreased susceptibility to cisplatin-induced toxicity of inner ear cells.
These findings support the notion that germline polymorphisms in Tpmt affect not only host tissue toxicity but also antitumor effectiveness.
suggestion that differential mouse TPMT activity is due to variation in mRNA expression
Of the 14 patients intolerant to thiopurines, NGS identified deleterious TPMT variants in 5 individuals whereas the biochemical test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%; specificity 93.75% and 50% respectively). SKAT-O test identified a significant association between MOCOS (zeige MOCOS ELISA Kits) gene and TPMT activity (p = 0.0015), not previously reported.
genetic association studies in cohort in Denmark: Data suggest that standard immunosuppression treatment failure in patients with autoimmune hepatitis is not associated with thiopurine S-methyltransferase genetic variants or HLA-DRB1 (zeige HLA-DRB1 ELISA Kits)*03 genotype in the population studied. (HLA-DRB1 (zeige HLA-DRB1 ELISA Kits) = major histocompatibility complex class II DR beta 1 (zeige HLA-DRB1 ELISA Kits))
This article reviews the thiopurine pharmacogenetics and the methods applied in common practice to evaluate patient's TPMT status. [review]
study aimed to determine the relationship between thiopurine metabolite levels and therapeutic response, and to investigate the association of NUDT15, TPMT, and thiopurine metabolites with leukopenia in patients with CD
TPMT*3C is overrepresented in acute lymphoblastic leukemia (ALL) cases in comparison with non-ALL group
The frequency of TPMT mutation in a homogeneous Sicilian cohort of patients with inflammatory bowel disease, autoimmune and hematological disorders was low. TPMT genotyping is not a sensitive tool for predicting thiopurine-induced leukopenia.
meta-analysis of three independent GWAS of TPMT activity; only genetic variants mapping to chromosome 6, including the TPMT gene region, were significantly associated with TPMT activity;finding is consistent with TPMT genotype being the primary determinant of TPMT activity
In a GWAS, TPMT activity in patients behaves as a monogenic trait, further bolstering the utility of TPMT genetic testing in the clinic
Review/Meta-analysis: thiopurine S-methyltransferase testing for averting drug toxicity.
A point mutation in the thiopurine S-methyltransferase gene that led to exon 5 deletion in the transcribed mRNA.
This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals. A pseudogene for this locus is located on chromosome 18q.
, Thiopurine S-methyltransferase
, S-adenosyl-L-methionine:thiopurine S-methyltransferase
, thiopurine methyltransferase
, NHL repeat containing 1