Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.67 (thiopurine methyltransferase)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe here the case of a 7-year old girl with lymphoma who developed life-threatening toxicities upon cytarabine plus mercaptopurine. Surprisingly, initial investigations on canonical thiopurine methyltransferase genetic polymorphism proved to be negative. We focused next on deregulations affecting the CDA gene implicated in the liver disposition of cytarabine. This patient was homozygous for both the 79A>C and the -31delC polymorphisms on the CDA gene and promoter, two genotypes with reported opposite effects on CDA phenotype. To determine the CDA status of this patient, additional functional testing was performed and eventually demonstrated that this patient was a poor metabolizer. This case demonstrates that besides affecting thiopurine methyltransferase, dysregulations with CDA should be screened to anticipate toxicities with the cytarabine plus mercaptopurine combination.
 ...
PMID:CDA deficiency as a possible culprit for life-threatening toxicities after cytarabine plus 6-mercaptopurine therapy: pharmacogenetic investigations. 2237 97

Certain interindividual differences affecting the efficacy of drug treatment and adverse drug reactions are caused by genetic variants, and their phenotypic effects differ among ethnic groups. In this study, we used whole exome sequencing (WES) systematically to identify germline mutations that influence the activities of drug-metabolizing enzymes, as well as that of a transporter. We analyzed DNA isolated from blood samples from 2,042 Japanese patients with diverse cancers. We identified sequence variants of CYP2B6 (rs3745274), CYP2C9 (rs1057910), CYP2C19 (rs4986893), CYP2C19 (rs4244285), TPMT (rs1142345), NAT2 (rs1799930), NAT2 (rs1799931), UGT1A1 (rs4148323), COMT (rs4680), ABCB1 (rs1045642), and CDA (rs60369023). Wider application of WES will help to determine the effects of mutations on the activities of proteins encoded by drug response genes, and the information gained will accelerate the development of personalized therapies for patients with cancer. Moreover, this knowledge may provide clues for preventing cancer before the onset of symptoms.
 ...
PMID:Whole exome sequencing detects variants of genes that mediate response to anticancer drugs. 2832 Oct 40