The renin-angiotensin system (RAS) has been implicated in the aetiology and treatment of depression [1]. Several common polymorphisms have been found in genes that encode for components of the renin-angiotensin system, for example the insertion/deletion polymorphism of the ACE gene and the M235T transversion of the angiotensinogen gene. Isolated studies have found an association between affective disorders and the ACE D allele [2] and the M allele of the M235T angiotensinogen gene [3] although other studies have found no significant associations (see [1]). The present study investigated a range of RAS-associated genes in Lebanese patients suffering from Major Depressive Disorder (MDD).

One hundred and forty-one patients satisfying DSM IV-R criteria for MDD along with 146 controls with no history of depression were recruited from a Lebanese population. Genomic DNA was extracted from buccal cells obtained by a cheek swab and amplified by polymerase chain reaction. Where appropriate, restriction fragment length polymorphism genotyping was then used, followed by identification of digested products by gel electrophoresis. The following common polymorphism frequencies were determined: angiotensinogen M235T, ACE I/D, AT₁ receptor A1166C and AT₂ receptor C3123A.

With the exception of the AT₁ receptor gene, all genotype frequencies fitted the Hardy-Weinburg Equilibrium. Although there was no significant difference in allele frequency between the groups, depressed patients and normal controls differed significantly in ACE I/D genotype frequency ( p = 0.018, χ² test), with an increased frequency of II and ID genotypes amongst depressed patients (Table 1). There were no other significant differences in genotype distributions between the populations. Importantly the observed genotype frequencies for the AT₁ receptor A1166C polymorphism differed significantly from values predicted by the Hardy-Weinburg equilibrium in the depressed population ( p = 0.047, χ² test).

Table 1
Distribution of ACE I/D polymorphisms in depressed patients and normal controls

The results are the first suggestion that that a depressed population may have an abnormal distribution of AT₁ receptor genotypes but whether such polymorphisms are predictive of patients responsive to the mood elevating effects of drugs such as ACE inhibitors remains to be explored. The results also support the work of others suggesting that there is not a robust association of ACE I/D nor angiotensinogen M235T genotype and psychiatric status across different populations.

1. Gard P R. Eur J Pharmacol 2002; 438: 1.
2. Arinami T. et al. Biol Psychiatry 1996; 40: 1122.
3. Miera-Lima IV, et al. Neurosci Lett 2000; 293: 103.