Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders

Herbert M. Lachman, Demitri F. Papolos, Takuya Saito, Yue Min Yu, Carol L. Szumlanski, Richard M. Weinshilboum

Research output: Contribution to journalArticle

1443 Scopus citations

Abstract

Catechol-O-methyltransferase (COMT) inactivates catecholamines and catechol drugs such as L-DOPA. A common genetic polymorphism in humans is associated with a three-to-fourfold variation in COMT enzyme activity and is also associated with individual variation in COMT thermal instability. We now show that this is due to G→A transition at codon 158 of the COMT gene that results in a valine to methionine substitution. The two alleles can be identified with a PCR-based restriction fragment length polymorphism analysis using the restriction enzyme NIa III. The identification of a genetic marker associated with significant alterations in enzyme activity will facilitate the analysis of a possible role for the COMT gene in neuropsychiatric conditions in which abnormalities in catecholamine neurotransmission are believed to occur, including mood disorders, schizophrenia, obsessive compulsive disorder, alcohol and substance abuse, and attention deficit hyperactivity disorder. In addition, this polymorphism may have pharmacogenetic significance in that it will help make it possible to identify patients who display altered metabolism of catechol drugs.

Original languageEnglish (US)
Pages (from-to)243-250
Number of pages8
JournalPharmacogenetics
Volume6
Issue number3
DOIs
StatePublished - Jul 19 1996

Keywords

  • Catechol
  • Methyltransferase
  • O-methyltransferase
  • Parkinson's disease
  • Velo cardio facial syndrome

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

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