The Val158Metrs4680 polymorphism does not appear to be involved in predisposition to suffer from migraine; however, this genetic factor may be involved in the phenotypic expression of chronic migraine, as anxiety, depression, and widespread pressure pain sensitivity were greater in those women with chronic, but not episodic, migraine with the Met/Met genotype.
Given that catechol-O-methyltransferase (COMT) is widely distributed in the hippocampus and its genetic variation is thought to contribute to the interindividual variability in pain perception and anxiety regulation, whether or not migraine and COMT val(158) met genotype have an interactive effect in the key brain area related to maladaptive stress, the hippocampus, is still poorly understood.
The rs4680 and rs4818 genotypic frequencies did not deviate from those expected for a population in Hardy-Weinberg equilibrium and did not correlate with demographics or clinical migraine features, even when considering migraine subtypes such as dopaminergic migraine, menstrual migraine, and menstrually related migraine .