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Gender influence on pharmacogenetic prediction of antidepressive efficacy
ACE is expressed in the CNS, where its function comprises the degradation of substance P (SP), which possibly influences the pathophysiology of depression. The ACE plasma concentration is determined by an I/D-polymorphism within the ACE gene. Thus, variations in CNS expression of ACE might influence antidepressant therapies.
We could show a divergent clinical outcome in relation to different genotypes in 153 depressed patients who were treated with various antidepressants. A lower HAM-D17 score after 4 weeks of treatment in D-allele-carriers was detected. Female patients with the homocygous I-allele had higher HAM-D17 scores before treatment and after four weeks. Male I/I-genotypes showed the contrary effects. An analysis of variance showed significant combined between subject effects of sex and ACE genotype on HAM-D17 scores (F[2, 153]=2.74, P=0.017).
Our investigations could indicate that the speed of onset of antidepressive therapies could be dependent on both gender and variants of the ACE gene.