Catechol-O-methyltransferase low activity genotype (COMT LL) is associated with low levels of COMT protein in human hepatocytes

Anne E.Sullivan Doyle, Julie E. Goodman, Paul M. Silber, James D. Yager

Research output: Contribution to journalArticlepeer-review

Abstract

A single nucleotide polymorphism in the COMT (catechol-O-methyltransferase) gene that alters the amino acid sequence at codon 108 of S-COMT from val to met (val108met polymorphism) has been associated with a number of diseases and neuropsychiatric disorders. Several studies have shown that the met108 allele (COMT L) is associated with three to four-fold lower levels of COMT activity, compared to the val108 allele (COMT H), in extracts of human erythrocytes, liver and kidney tissue. We hypothesized that the differences in COMT activity observed in these studies were due to differing levels of COMT protein in cells and tissues with varying COMT genotypes. In order to address this, we obtained hepatocytes from 31 Caucasian female donors and determined their COMT genotype, COMT activity and COMT protein levels. We found that both cytosolic COMT activity and cytosolic COMT protein levels are lower in hepatocytes from COMT LL individuals, and that COMT activity levels correlate with COMT protein levels. Therefore, lower COMT activity seen in tissues and cells with the COMT LL genotype is likely due to lower COMT protein levels compared with tissues and cells from COMT HH individuals.

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalCancer Letters
Volume214
Issue number2
DOIs
StatePublished - Oct 28 2004

Keywords

  • Enzyme activity
  • Gene polymorphism
  • Human hepatocytes
  • val108met COMT

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Catechol-O-methyltransferase low activity genotype (COMT <sup>LL</sup>) is associated with low levels of COMT protein in human hepatocytes'. Together they form a unique fingerprint.

Cite this