Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine (DA), epinephrine, and norepinephrine as well as tightly regulating DA in the prefrontal cortical areas (1–3). The gene encoding COMT contains a well-studied single nucleotide polymorphism (SNP) that results in the presence of methionine (Met) or valine (Val) at codon 108 (in s-COMT) or codon 158 (in m-COMT) (4). The Val-coded allele is 3 to 4 times more active than the Met-coded allele, resulting in reduced DA levels in the synapse (5, 6). The COMT Val158Met variation has been widely researched for many phenotypes of psychiatric disorders including depression (7), psychosis (8), and drug addiction (9). Given the key role of DA in mediating drug reward, drug-seeking, and withdrawal states, studying the COMT Val158Met variation is especially important for addictive disorders, including nicotine addiction (10).
