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

Elevated plasma total homocysteine (tHcy) is a risk factor for various disorders. We investigated whether functional polymorphisms in catechol‐O‐methyltransferase (COMT) influence tHcy, since COMT activity produces S‐adenosylhomocysteine (SAH), a homocysteine precursor. We hypothesized that high act...

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Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2008-09, Vol.147B (6), p.996-999
Main Authors: Tunbridge, Elizabeth M., Harrison, Paul J., Warden, Donald R., Johnston, Carole, Refsum, Helga, Smith, A. David
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Aged
Aged, 80 and over
Alleles
Biological and medical sciences
Case-Control Studies
Catechol O-Methyltransferase - genetics
Epistasis, Genetic
Female
Genotype
Homocysteine - blood
Humans
Linkage Disequilibrium
Male
Medical genetics
Medical sciences
methylation
methylenetetrahydrofolate reductase
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Middle Aged
Models, Biological
Polymorphism, Single Nucleotide - physiology
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
S-adenosylhomocysteine
S-adenosylmethionine
Schizophrenia
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Summary:Elevated plasma total homocysteine (tHcy) is a risk factor for various disorders. We investigated whether functional polymorphisms in catechol‐O‐methyltransferase (COMT) influence tHcy, since COMT activity produces S‐adenosylhomocysteine (SAH), a homocysteine precursor. We hypothesized that high activity COMT variants would be associated with high tHcy, since they presumably result in increased formation of SAH. We genotyped 780 community‐dwelling elderly individuals for functional COMT (Val158Met and A−287G) and methylenetetrahydrofolate reductase (MTHFR; C677T) polymorphisms, and measured plasma tHcy. As predicted, COMT Val158 carriers had significantly higher tHcy than Met158 homozygotes. The effect was limited to individuals homozygous for the MTHFR T677 allele. In addition, individuals homozygous for the COMT G−287 allele tended to have lower tHcy levels. High activity variants of COMT interact with the low activity variant of MTHFR to increase tHcy levels. The effect on tHcy may contribute to the reported associations of COMT genotype with psychiatric and neurobiological phenotypes. The results also indicate that COMT activity may influence a broader range of biochemical pathways than hitherto appreciated. © 2008 Wiley‐Liss, Inc.
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.30700