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Polymorphisms in the catechol‐ O ‐methyltransferase (COMT) gene influence plasma total homocysteine levels
Author(s) -
Tunbridge Elizabeth M.,
Harrison Paul J.,
Warden Donald R.,
Johnston Carole,
Refsum Helga,
Smith A. David
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30700
Subject(s) - methylenetetrahydrofolate reductase , catechol o methyl transferase , homocysteine , methyltransferase , genotype , allele , medicine , endocrinology , genetics , biology , gene , methylation
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 (Val 158 Met and A −287 G) and methylenetetrahydrofolate reductase ( MTHFR ; C 677 T) polymorphisms, and measured plasma tHcy. As predicted, COMT Val 158 carriers had significantly higher tHcy than Met 158 homozygotes. The effect was limited to individuals homozygous for the MTHFR T 677 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.