PMID- 10331075
OWN - NLM
STAT- MEDLINE
DCOM- 19990709
LR  - 20071114
IS  - 0362-1642 (Print)
IS  - 0362-1642 (Linking)
VI  - 39
DP  - 1999
TI  - Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine
      methyltransferase, and histamine N-methyltransferase.
PG  - 19-52
AB  - Methyl conjugation is an important pathway in the biotransformation of many
      exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase 
      enzymes have resulted in the identification and characterization of functionally 
      important common genetic polymorphisms for catechol O-methyltransferase,
      thiopurine methyltransferase, and histamine N-methyltransferase. In recent years,
      characterization of these genetic polymorphisms has been extended to include the 
      cloning of cDNAs and genes, as well as a determination of the molecular basis for
      the effects of inheritance on these methyltransferase enzymes. The thiopurine
      methyltransferase genetic polymorphism is responsible for clinically significant 
      individual variations in the toxicity and therapeutic efficacy of thiopurine
      drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase 
      genetic polymorphism represents one of the first examples in which testing for a 
      pharmacogenetic variant has entered standard clinical practice. The full
      functional implications of pharmacogenetic variation in the activities of
      catechol O-methyltransferase and histamine N-methyltransferase remain to be
      determined. Finally, experimental strategies used to study methylation
      pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic,
      molecular, and genomic approaches that have been used to determine the role of
      inheritance in variation in drug metabolism, effect, and toxicity.
FAU - Weinshilboum, R M
AU  - Weinshilboum RM
AD  - Department of Pharmacology, Mayo Medical School/Mayo Clinic/Mayo Foundation,
      Rochester, Minnesota 55905, USA. weinshilboum.richard@mayo.edu
FAU - Otterness, D M
AU  - Otterness DM
FAU - Szumlanski, C L
AU  - Szumlanski CL
LA  - eng
GR  - R01 GM28157/GM/NIGMS NIH HHS/United States
GR  - R01 GM35720/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Annu Rev Pharmacol Toxicol
JT  - Annual review of pharmacology and toxicology
JID - 7607088
RN  - 0 (Pharmaceutical Preparations)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
RN  - EC 2.1.1.67 (thiopurine methyltransferase)
RN  - EC 2.1.1.8 (Histamine N-Methyltransferase)
SB  - IM
MH  - Animals
MH  - Catechol O-Methyltransferase/genetics/*metabolism
MH  - Histamine N-Methyltransferase/genetics/*metabolism
MH  - Humans
MH  - Methylation
MH  - Methyltransferases/genetics/*metabolism
MH  - Pharmaceutical Preparations/metabolism
RF  - 157
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - 10.1146/annurev.pharmtox.39.1.19 [doi]
PST - ppublish
SO  - Annu Rev Pharmacol Toxicol. 1999;39:19-52. doi: 10.1146/annurev.pharmtox.39.1.19.