It is a reasonable conjecture that dopamine metabolism may be related to CIP. A VNTR polymorphism in the dopamine transporter gene (SLC6A3) and variants in the dopamine β-hydroxylase gene (DBH) have previously been shown to be associated with CIP (Cubells et al., 2000; Gelernter et al., 1994; Kalayasiri et al., 2006b). The dopamine transporter protein directly regulates the concentration of dopamine in the synaptic cleft by reuptake to the presynaptic neuron. The enzyme dopamine β-hydroxylase converts dopamine to norepinephrine. The COMT enzyme plays a role in the same pathways by metabolizing dopamine and norepinephrine. Therefore, the association of COMT with CIP is mechanistically consistent with earlier reports by virtue of having an impact on dopaminergic and noradrenergic neurotransmission. This study identifies a third important enzyme in catecholamine metabolism that may be related to CIP, and this should aid in our understanding of the pathophysiology of this trait.
