What is Catechol-O-Methyltransferase Val158Met Polymorphism?
Catechol-O-methyltransferase is a phase-II enzyme that catalyses the transfer of a methyl group from S-adenosylmethionine to catechol substrates, thereby inactivating catecholamines — dopamine, adrenaline, and noradrenaline — and catechol oestrogens. The rs4680 single-nucleotide polymorphism causes a valine-to-methionine substitution at codon 158 of the membrane-bound isoform (codon 108 of the cytosolic form). The Val158 variant exhibits roughly three- to four-fold higher enzymatic activity at physiological temperature than Met158, leading to faster degradation of dopamine in the prefrontal cortex and other tissues. This SNP is one of the most extensively studied functional polymorphisms in neuroscience and pharmacogenomics.