Background: During normal aging dopaminergic neuromodulation declines and this has been associated with impaired cognitive function and negative and positive affects. A common polymorphism (rs4680; Val/Met) in the enzyme catechol-O6-methyltransferase (COMT) gene is a determinant of the rate of elimination of dopamine and noradrenaline in the prefrontal cortex, and is therefore thought to modulate dopaminergic signaling.
The aim of the present study was to test whether subjective well-being (SWB) was influenced by interactions between COMT rs4680 genotype, sex, physical activity (PA), and serum biomarkers of somatic health.
Methods: We studied 389 community dwelling, socially active seniors, mean age 74 years and M/F 127/262 (AS cohort). COMT was genotyped by pyrosequencing, PA was assessed by the IPAQ-E, and SWB by the PGWB index.
Results: Male carriers of the rs4680 Met-allele had significantly better SWB than subjects with the ancestral wildtype Val/Val (p=0.009), also when adjusting for age, homocysteine, HbA1c, cystatin C, and IPAQ-E score (p=3.8×10 -5). There was a strong interaction between PA and the rs4680 polymorphism (p=0.001). In women on the other hand the COMT genotype was unrelated to PGWB sum and its subdimensions,
Conclusion: In socially active, elderly retired men, COMT genotype has a major influence on SWB, partly mediated by an interaction with physical activity. This finding should help implementing better public health intervention strategies by tailoring the interventions at appropriately selected subgroups.