Individuals carrying the short allele of a common polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) exhibit heightened amygdala responses to passive stimulation with aversive emotional material. In turn, the level of amygdala activation in response to emotion can be decreased by will, for example by using cognitive emotion regulation strategies. In the present study, 37 female subjects (s-carriers: n= 21; l/l-homozygotes: n= 16) performed an emotion regulation task during functional magnetic resonance imaging to determine whether cognitive emotion regulation can modulate the genetically determined amygdala hyperreactivity in 5-HTTLPR short allele carriers. Our results demonstrate that cognitive emotion regulation diminishes the difference in amygdala reactivity to threat-related stimuli between 5-HTTLPR genotype groups. Furthermore, we also provide evidence that the effect of cognitive regulation is mediated through altered coupling between the amygdala and prefrontal regulatory regions. Our findings demonstrate that while the presence of the 5-HTTLPR short allele leads to heightened responses in the amygdala, cognitive regulation can modify genetically mediated effects upon brain function by volitionally altering prefrontal-amygdala connectivity.