Редактирование: TPMT

Thiopurine S-methyltransferase (EC 2.1.1.67) (Thiopurine methyltransferase)

==Publications==

{{medline-entry
|title=Pre-analytic and analytic sources of variations in thiopurine methyltransferase activity measurement in patients prescribed thiopurine-based drugs: A systematic review.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21402061
|abstract=Low thiopurine S-methyltransferase ([[TPMT]]) enzyme activity is associated with increased thiopurine drug toxicity, particularly myelotoxicity. Pre-analytic and analytic variables for [[TPMT]] genotype and phenotype (enzyme activity) testing were reviewed. A systematic literature review was performed, and diagnostic laboratories were surveyed. Thirty-five studies reported relevant data for pre-analytic variables (patient age, gender, race, hematocrit, co-morbidity, co-administered drugs and specimen stability) and thirty-three for analytic variables (accuracy, reproducibility). [[TPMT]] is stable in blood when stored for up to 7 days at room temperature, and 3 months at -30°C. Pre-analytic patient variables do not affect [[TPMT]] activity. Fifteen drugs studied to date exerted no clinically significant effects in vivo. Enzymatic assay is the preferred technique. Radiochemical and HPLC techniques had intra- and inter-assay coefficients of variation (CVs) below 10%. [[TPMT]] is a stable enzyme, and its assay is not affected by age, gender, race or co-morbidity.
|mesh-terms=* Aging
* Azathioprine
* Enzyme Stability
* Health Care Surveys
* Hematocrit
* Humans
* Mercaptopurine
* Methyltransferases
* Prescription Drugs
* Purines
* Sex Characteristics
* Thioguanine

|full-text-url=https://sci-hub.do/10.1016/j.clinbiochem.2011.03.022
}}
{{medline-entry
|title=Erythrocyte fraction affects red blood cell thiopurine methyltransferase activity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/8582469
|abstract=Red blood cell (RBC) thiopurine methyltransferase ([[TPMT]]) metabolizes the cytotoxic drugs 6-mercaptopurine and azathioprine. RBC [[TPMT]] activity has been reported to predict clinical outcome in children with acute lymphoblastic leukaemia and in kidney transplant patients. We first suspected that the erythrocyte fraction affected the calculated [[TPMT]] activity when we examined intraindividual [[TPMT]] activities in kidney transplant recipients. We demonstrated that the erythrocyte fraction affected the calculated [[TPMT]] activity, thus causing a methodological inaccuracy. A low erythrocyte fraction gave an erroneously low [[TPMT]] activity. Mean variation of 7.0% was observed within the normal limits of the haematocrit level in healthy subjects. The slopes of the [[TPMT]] activity between erythrocyte fraction 0.1 and 0.5 were all significantly different from zero, and the activity displayed good linearity from erythrocyte fraction 0.2. There was a strong association between [[TPMT]] activity and erythrocyte fraction in a population sample of children, but not in two other population samples. We propose that the [[TPMT]] assay should be performed in lysates at a standardized erythrocyte fraction to avoid variation in activity due to the range of the haematocrit in a population.
|mesh-terms=* Adult
* Aged
* Aging
* Child
* Erythrocytes
* Humans
* In Vitro Techniques
* Methyltransferases
* Subcellular Fractions

|full-text-url=https://sci-hub.do/10.1007/BF00194340
}}
{{medline-entry
|title=Higher activity of polymorphic thiopurine S-methyltransferase in erythrocytes from neonates compared to adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/8563768
|abstract=Thiopurine S-methyltransferase ([[TPMT]]) catalyses the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including thiopurine antimetabolites (i.e. mercaptopurine and thioguanine). The activity of [[TPMT]] in erythrocytes and other tissues exhibits genetic polymorphism, which is inherited as an autosomal codominant trait. Although inheritance is the principal determinant of [[TPMT]] activity, other factors (e.g. renal function, race and thiopurine therapy) have been shown to influence erythrocyte [[TPMT]] activity. Because the [[TPMT]] polymorphism has not been established in early erythrocyte populations, and the activity of many enzymes differs in neonates, we determined the activity of [[TPMT]] in erythrocytes obtained from 60 full-term newborns. Median peripheral blood [[TPMT]] activity was 25.3 U per ml pRBC (range 9-52.8 U per ml pRBC), which was > 50% higher than race matched healthy adults (p < 0.001). Western blot analysis demonstrated higher [[TPMT]] protein content in erythrocytes from newborns compared to adults, and revealed a significant correlation between [[TPMT]] protein and [[TPMT]] activity in erythrocytes (rs = 0.63, p = 0.03). Although erythrocyte [[TPMT]] activity was significantly higher in newborns, the distribution of activity in newborns was consistent with the genetic polymorphism previously observed in adults.
|mesh-terms=* Adult
* African Continental Ancestry Group
* Aging
* Blotting, Western
* Erythrocytes
* European Continental Ancestry Group
* Fetal Blood
* Humans
* Infant, Newborn
* Methyltransferases
* Polymorphism, Genetic
* Reference Values
* United States

|full-text-url=https://sci-hub.do/10.1097/00008571-199510000-00003
}}
{{medline-entry
|title=Thiopurine methyltransferase regulation in rat kidney: immunoprecipitation studies.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/1897245
|abstract=1. Thiopurine methyltransferase ([[TPMT]]) catalyses the S-methylation of thiopurine drugs. [[TPMT]] activity in the kidneys of male Sprague-Dawley (S-D) rats is approximately twice that present in the kidneys of female S-D rats, and this difference is testosterone-dependent. Renal [[TPMT]] activities in these animals also increase dramatically during growth and development. 2. Our studies were conducted to determine whether variations in TMPT activity in the S-D rat kidney were due to differences in the quantity of [[TPMT]] protein. Rabbit polyclonal antibodies to partially purified rat kidney [[TPMT]] were used to develop an immunoprecipitation assay for immunoreactive [[TPMT]] protein. 3. Gender-related differences in renal [[TPMT]] activities in S-D rats were due to a lower content of immunoreactive [[TPMT]] protein in kidneys of female animals. [[TPMT]] enzyme activities and immunoreactive protein levels were also directly correlated in renal preparations from castrated and sham-operated male rats, from testosterone-treated castrated and sham-operated male rats, and from testosterone-treated and control female rats. 4. There was also a significant positive correlation between [[TPMT]] enzymic activities and immunoreactive [[TPMT]] protein levels in renal tissue from different aged male S-D rats (rs = 0.955, n = 15, P less than 0.001.) 5. These results demonstrate that changes in S-D kidney [[TPMT]] activity during growth and development, in the two sexes and in response to testosterone, were due to variations in the quantity of immunoreactive [[TPMT]] protein.
|mesh-terms=* Aging
* Animals
* Animals, Newborn
* Female
* Kidney
* Male
* Methyltransferases
* Orchiectomy
* Precipitin Tests
* Rats
* Sex Characteristics
* Testosterone

|full-text-url=https://sci-hub.do/10.3109/00498259109039485
}}