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Polymorphisms in the catechol-O-methyltransferase (COMT) gene influence plasma total homocysteine levels

Elizabeth M Tunbridge1, Paul J Harrison, Donald R Warden

  • 1Department of Psychiatry, University of Oxford, Oxford, United Kingdom. elizabeth.tunbridge@psych.ox.ac.uk

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
|January 15, 2008
PubMed

Insights

High activity catechol-O-methyltransferase (COMT) gene variants are linked to elevated total homocysteine (tHcy) levels, particularly in individuals with specific methylenetetrahydrofolate reductase (MTHFR) genotypes. This interaction may influence health outcomes.

Area of Science:

  • Biochemistry
  • Genetics
  • Neuroscience

Background:

  • Elevated plasma total homocysteine (tHcy) is a known risk factor for various health disorders.
  • Catechol-O-methyltransferase (COMT) enzyme activity generates S-adenosylhomocysteine (SAH), a precursor to homocysteine.

Purpose of the Study:

  • To investigate the influence of functional polymorphisms in the COMT gene on plasma tHcy levels.
  • To test the hypothesis that high-activity COMT variants are associated with increased tHcy due to enhanced SAH production.

Main Methods:

  • Genotyping of 780 elderly individuals for COMT (Val158Met, A-287G) and MTHFR (C677T) polymorphisms.
  • Measurement of plasma tHcy levels in all participants.

Main Results:

  • COMT Val158 carriers exhibited significantly higher tHcy compared to Met158 homozygotes.
  • This association was significant only in individuals homozygous for the MTHFR T677 allele.
  • COMT G-287 homozygotes showed a trend towards lower tHcy levels.
  • High-activity COMT variants interact with the low-activity MTHFR T677 variant to elevate tHcy.

Conclusions:

  • Functional COMT polymorphisms, particularly the Val158Met variant, significantly influence plasma tHcy levels in an MTHFR genotype-dependent manner.
  • These findings suggest COMT's role in homocysteine metabolism and potential implications for psychiatric and neurobiological phenotypes.
  • COMT activity may impact a wider array of biochemical pathways than previously understood.

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