Catechol-O-methyltransferase (COMT) plays a major role in brain catecholamine metabolism by catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to catecholamines. COMT maps to chromosome 22q11.21-q11.23, a region of particular interest because it is frequently included in the velocardiofacial syndrome (VCFS) deletion region (Grossman et al. 1992) Numerous genetic associations have been reported to several single nucleotide polymorphism (SNPs) or haplotypes at the COMT locus. These include VCFS-related traits (Bearden et al., 2005; Bearden et al.,2004; Gothelf et al., 2005; Gothelf et al.,2006; Lachman et al., 996), schizophrenia (Lachman et al., 1996; Shifman et al., 2002), anxiety-related personality traits (Stein et al., 2005), pain sensitivity (Diatchenko et al., 2005; Nackley et al., 2006), psychological stress response (Jabbi et al., 2007), and nicotine dependence (Beuten et al.,2006; Guo et al., 2007), among other traits. COMT haplotypes code for varying COMT enzymatic activity (Diatchenko et al., 2005), and associate with variation in mRNA structure and stability (Nackley et al., 2006).
