AN INSERTION DELETION POLYMORPHISM IN THE ANGIOTENSIN-CONVERTING ENZYME GENE IS ASSOCIATED WITH BOTH BRAIN SUBSTANCE-P CONTENTS AND AFFECTIVE-DISORDERS/

Because of a potent action of angiotensin converting enzyme (ACE) to d egrade substance P (SP) and an association of the insertion/deletion ( I/D) polymorphism of the ACE gene with ACE activity, an association be tween the SP level and the ACE I/D polymorphism were examined using 20 human postmortem brain samples. The results showed a significant asso ciation between the polymorphism and SP levels in the basal ganglia an d substantia nigra, where both ACE and SP concentrate, and a higher SP level in the subjects with the DD genotype than in those with the II genotype, with an intermediate level in heterozygotes. Associations of the polymorphism with schizophrenia and affective disorders were also investigated in 292 unrelated Japanese schizophrenics, 65 patients wi th affective disorders, and 579 controls. The D allele was significant ly more frequent in the patients with affective disorders than in the controls (p < .02), and the DD genotype was significantly more frequen t in the patients with affective disorders than in the controls (p < . 002). There is no significant difference in the frequencies of the all ele and the genotype between the controls and schizophrenics. These re sults suggest that the ACE I/D polymorphism is one of the genetic fact ors for an interindividual variability of brain SP levels, and that th e ACE polymorphism may contribute to the susceptibility to affective d isorders. (C) 1996 Society of Biological Psychiatry