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https://www.readbyqxmd.com/read/29534852/association-between-tpmt-3c-and-decreased-thiopurine-s-methyltransferase-activity-in-patients-with-neuromyelitis-optica-spectrum-disorders-in-china
#1
Xiaoqing Gong, Shenghui Mei, Xindi Li, Xingang Li, Heng Zhou, Yonghong Liu, Anna Zhou, Li Yang, Zhigang Zhao, Xinghu Zhang
Thiopurines (TPRs) are effective drugs in treating neuromyelitis optica spectrum disorders (NMOSD) and other diseases. TPRs' toxicity is mainly imputed to thiopurine S-methyltransferase (TPMT) activity. In Chinese population, the most common and important variation of TPMT is TPMT*3C (rs1142345). This study aims to reveal the association between TPMT activity and genetic polymorphisms of TPMT in patients with NMOSD in China. An LC-MS/MS method was used to evaluate the TPMT activity by using 6-mercapthioprine as substrate in human erythrocyte hemolysate via 1 h incubation at 37 °C to form its methylated product 6-methylmercaptopurine (6-MMP)...
March 10, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29491687/comparison-of-tpmt-and-nudt15-polymorphisms-in-chinese-patients-with-inflammatory-bowel-disease
#2
Hong-Hui Wang, Ying He, Hong-Xian Wang, Cheng-Ling Liao, Yu Peng, Li-Jian Tao, Wei Zhang, Hui-Xiang Yang
AIM: To observe gene polymorphisms of TPMT and NUDT15 , and compare their predictive value for azathioprine (AZA)-induced leukopenia in inflammatory bowel disease (IBD). METHODS: This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital, Central South University, Changsha, China from February 2016 to November 2017. Peripheral blood of all patients was collected to detect their genotypes of TPMT and NUDT15 by pyrosequencing at the Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital...
February 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29470173/preemptive-nudt15-genotyping-redefining-the-management-of-patients-with-thiopurine-induced-toxicity
#3
Swarup A V Shah, Minal U Paradkar, Devendra C Desai, Tester F Ashavaid
BACKGROUND: Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between the NUDT15 gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of the NUDT15 variant (C415T) in Indian patients on thiopurine therapy. METHODS: NUDT15 and TPMT genotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique...
March 28, 2018: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/29444714/thiopurine-s-methyltransferase-activity-in-nigerians-phenotypes-and-activity-reference-values
#4
Ayorinde Adehin, Oluseye O Bolaji
OBJECTIVES: This study assessed the activity of thiopurine S-methyltransferase (TPMT) in Nigerians with a view to providing data on susceptibility to thiopurine toxicity, and as well generate reference activity values for clinical use. RESULTS: TPMT activity, expressed as the amount of 6MMP in ng/mL after 1 h incubation at 37 °C per haemoglobin (U/g Hb), varied between 2.34 and 63.50 U/g Hb in the study population. Poor metabolic phenotypes, characterised by an activity values below 8...
February 14, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29436076/mrna-expression-of-drug-metabolism-enzymes-and-transporter-genes-at-birth-using-human-umbilical-cord-blood
#5
Virginia Neyro, Valéry Elie, Yves Médard, Evelyne Jacqz-Aigrain
Growth and maturation changes are mainly responsible for differences in drug pharmacokinetics and pharmacodynamics observed between adults and children, especially neonates. Ontogeny of drug metabolizing enzymes and transporters play an important role in drugs inter-individual pharmacokinetic variability but data are limited in both term and preterm neonates. This study aimed to characterize mRNA expression of the main drug metabolizing enzymes and transport proteins involved in drug disposition, using umbilical cord blood (UCB), according to gender, gestational age and genetic background...
February 13, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29425801/analytical-and-clinical-validation-of-an-lc-ms-ms-method-to-measure-thiopurine-s-methyltransferase-activity-by-quantifying-d3-6-mmp
#6
Jing Ma, Christiaan W Sies, Linda S Pike
BACKGROUND: Identification of patients with thiopurine S-methyltransferase (TPMT) deficiency prior to thiopurine drug therapy has become routine clinical practice worldwide. To measure TPMT activity, traditional radiochemical assays have been replaced by chromatographic methods. METHOD: Inspired by the increasing number of isotope labelled sources that may be of benefit for the TPMT assay, a new LC-MS/MS method for TPMT activity was developed and validated. Isotope labelled d3-S-adenosyl-l-methionine (d3-SAM) was selected for the enzymatic methylation of mercaptopurine during sample incubation; d3-6-methylmercaptopurine (d3-6-MMP) with d2-2, 8-hypoxanthine as the internal standard was quantified to ascertain individual TPMT activity...
February 6, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29421584/effective-long-term-solution-to-therapeutic-remission-in-inflammatory-bowel-disease-role-of-azathioprine
#7
REVIEW
Lyla Adam, Alisa Phulukdaree, Prashilla Soma
Azathioprine (AZA) is a well-known immunosuppressant used for many years for its ability to ensure long term disease remission in inflammatory bowel diseases (IBD) at an affordable cost to the public. However, the side effect profile has raised many concerns with numerous investigations into the risk, cause and prevention of these effects. Much of the side effect profile of AZA can be linked to a single nucleotide polymorphism (SNP) in the thiopurine methyltransferase (TPMT) gene which ensures the breakdown and efficacy of AZA...
February 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29398872/influence-of-nudt15-variants-on-hematological-pictures-of-patients-with-inflammatory-bowel-disease-treated-with-thiopurines
#8
Yuichiro Kojima, Yosuke Hirotsu, Wataru Omata, Makoto Sugimori, Shinya Takaoka, Hiroshi Ashizawa, Keiko Nakagomi, Dai Yoshimura, Kenji Hosoda, Yoji Suzuki, Hitoshi Mochizuki, Masao Omata
AIM: The single nucleotide polymorphism (SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn's disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease (IBD) treated with thiopurines. METHODS: Ninety-six Japanese patients with IBD were enrolled...
January 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29387964/role-of-tpmt-and-itpa-variants-in-mercaptopurine-disposition
#9
Tina Gerbek, Maria Ebbesen, Jacob Nersting, Thomas L Frandsen, Malin Lindqvist Appell, Kjeld Schmiegelow
PURPOSE: To explore the levels of thioguanine incorporated into DNA (DNA-TG), and erythrocyte levels of 6-thioguanine nucleotides (Ery-TGN) and methylated metabolites (Ery-MeMP) during 6-mercaptopurine (6MP)/Methotrexate (MTX) therapy of childhood acute lymphoblastic leukemia (ALL) and the relation to inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT) gene variants. METHODS: Blood samples were drawn during 6MP/MTX maintenance therapy from 132 children treated for ALL at Rigshospitalet, Copenhagen...
February 1, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29373914/genetic-polymorphism-of-thiopurine-s-methyltransferase-in-children-with-acute-lymphoblastic-leukemia-in-jordan
#10
Mervat Alsous, Al-Motassem Yousef, Mariam Abdel Jalil, Mohammed Zawiah, Shorouq Yacoub, Deema Momani, Alia Gharabli, Suha Omar, Rawad Rihani
Background and Aims: It has been demonstrated that homozygote and heterozygote mutant allele carriers for thiopurine S-methyltransferase (TPMT) are at high risk of developing myelosuppression after receiving standard doses of 6-mercaptopurine (6-MP). The aim of this study was to determine the frequency of TPMT deficient alleles in children with acute lymphoblastic leukemia (ALL) in Jordan and to compare it with other ethnic groups. Methods: We included 52 ALL childhood cases from King Hussein Cancer Research Center in Jordan...
January 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29370945/-usefulness-of-thiopurine-methyltransferase-polymorphism-study-and-metabolites-measurement-for-patients-treated-by-azathioprine
#11
V Guillotin, G Galli, J-F Viallard
Azathioprine is widely used in internal medicine and frequently implicated in occurrence of adverse events. Among these adverse events the bone marrow suppression, a dose-related one, is the most serious because of is potential morbidity and mortality. Severe myelosuppression, associated with abnormal AZA metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic polymorphism that results in a high variability of its activity with 89% of patients with a normal activity, 11% with an intermediate activity, and 0...
January 19, 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29357999/recommendations-of-the-spanish-working-group-on-crohn-s-disease-and-ulcerative-colitis-geteccu-on-the-use-of-tiopurines-in-inflammatory-bowel-disease
#12
Fernando Bermejo, Mariam Aguas, María Chaparro, Eugeni Domènech, Ana Echarri, Esther Garcia-Planella, Iván Guerra, Javier P Gisbert, Antonio López-Sanromán
Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects...
January 18, 2018: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/29351371/implementation-of-standardized-clinical-processes-for-tpmt-testing-in-a-diverse-multidisciplinary-population-challenges-and-lessons-learned
#13
Kristin W Weitzel, D Max Smith, Amanda R Elsey, Benjamin Q Duong, Benjamin Burkley, Michael Clare-Salzler, Yan Gong, Tara A Higgins, Benjamin Kong, Taimour Langaee, Caitrin W McDonough, Benjamin J Staley, Teresa T Vo, Dyson T Wake, Larisa H Cavallari, Julie A Johnson
Although thiopurine S-methyltransferase (TPMT) genotyping to guide thiopurine dosing is common in the pediatric cancer population, limited data exist on TPMT testing implementation in diverse, multidisciplinary settings. We established TPMT testing (genotype and enzyme) with clinical decision support, provider/patient education, and pharmacist consultations in a tertiary medical center and collected data over 3 years. During this time, 834 patients underwent 873 TPMT tests (147 (17%) genotype, 726 (83%) enzyme)...
March 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29350448/clinical-and-genetic-associations-for-carboplatin-related-ototoxicity-in-children-treated-for-retinoblastoma-a-retrospective-noncomparative-single-institute-experience
#14
Sameh E Soliman, Crystal N D'Silva, Helen Dimaras, Irakli Dzneladze, Helen Chan, Brenda L Gallie
BACKGROUND: Children with retinoblastoma treated with carboplatin chemotherapy risk moderate to severe, irreversible hearing loss. Based on published evidence, we hypothesized that ototoxicity risk is associated with clinical parameters and variants in candidate genes in drug metabolism pathways (methyltransferases [thiopurine S-methyltransferase, TPMT] and [catechol-O-methyltransferase, COMT], and drug transporter ABCC3). PROCEDURE: We retrospectively reviewed clinical records of patients with retinoblastoma treated with carboplatin chemotherapy regarding age (at diagnosis and chemotherapy initiation), chemotherapy sessions (cycles number, drug doses, and cumulative carboplatin dose), and hearing loss (defined as ototoxicity ≥grade 2 by at least one classification system)...
May 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29327413/itpa-activity-in-children-treated-by-azathioprine-relationship-to-the-occurrence-of-adverse-drug-reactions-and-inflammatory-response
#15
Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin, Alain Lachaux, Roselyne Boulieu
Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological diseases such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reactions (ADRs) and drug response is observed. This study investigated (i) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, and (ii) the relationship between ITPA activity and the inflammatory activity observed in children with IBD...
January 11, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29321348/influence-of-thiopurine-methyltransferase-gene-polymorphism-on-egyptian-children-with-acute-lymphoblastic-leukaemia
#16
Azza A G Tantawy, Fatma S E Ebeid, Amira A M Adly, Eman El-Ghoroury, Mai Mostafa
Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29226420/editorial-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype-the-perils-of-ageing-authors-reply
#17
EDITORIAL
M M T J Broekman, G J Wanten, D J de Jong
No abstract text is available yet for this article.
January 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29226409/editorial-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype-the-perils-of-ageing
#18
EDITORIAL
A J Willington, R B Gearry
No abstract text is available yet for this article.
January 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29210335/predictive-role-of-nudt15-variants-on-thiopurine-induced-myelotoxicity-in-asian-inflammatory-bowel-disease-patients
#19
Natalia Sutiman, Sylvia Chen, Khoon Lin Ling, Sai Wei Chuah, Wai Fook Leong, Vinayak Nadiger, Madeline Tjai, Chris San Choon Kong, Brian John Schwender, Webber Chan, Hang Hock Shim, Wee Chian Lim, Chiea Chuen Khor, Yin Bun Cheung, Balram Chowbay
BACKGROUND: Genetic variants of TPMT and NUDT15 have been reported to predict the inter-patient variability in response and toxicity profiles of patients receiving thiopurine therapy. However, the clinical utility of TPMT genotyping in guiding thiopurine doses has been questionable, in part due to underlying differences in the prevalence of TPMT variants in both Caucasian and Asian populations. Several NUDT15 variants have been associated with thiopurine-induced leukopenia, particularly in Asian cohorts...
January 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29206869/measurements-of-6-thioguanine-nucleotide-levels-with-tpmt-and-nudt15-genotyping-in-patients-with-crohn-s-disease
#20
Ji Hyeon Lee, Tae Jun Kim, Eun Ran Kim, Sung Noh Hong, Dong Kyung Chang, Li-Hwa Choi, Hye In Woo, Soo-Youn Lee, Young-Ho Kim
The association between the 6-thioguanine nucleotide (6-TGN) level and clinical remission in Crohn's disease (CD) remains controversial. Thiopurine-induced leukopenia is a life-threatening complication of CD in Asians that was recently shown to strongly correlate with NUDT15 genetic variants. This 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...
2017: PloS One
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