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J Affect Disord. 2012 Feb;136(3):971-8. doi: 10.1016/j.jad.2011.08.019. Epub 2011 Oct 28.

The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis.

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Department of Neuropsychiatry, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, PR China.



The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene has been implicated in susceptibility to major depressive disorder (MDD) and its treatment response; however, a large number of studies have reported inconsistent results. The aim of this study is to examine the role of I/D polymorphism of ACE gene in MDD risk and its treatment response by a case-control study and meta-analysis.


Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder and 371 normal controls were recruited for the study. We searched Pubmed, Embase, CNKI, Wanfang, and Weipu database, covering all papers until March 31, 2011. Statistical analysis was performed using the software STATA 10.0.


Genotype and allele distributions of ACE I/D were not significantly different between case and control groups. No significant association with treatment response was discovered. A total of 2479 cases and 7744 controls in 15 case-control studies were included in this meta-analysis. The results indicated that the D/D homozygote carriers had an 18% increased risk of MDD, when compared with the homozygotes I/I and heterozygote I/D [odds ratio (OR)=1.18, 95% confidence interval (CI):1.04-1.33]. In the subgroup analysis, significant elevated risks were associated with D/D homozygote carriers in Caucasians (OR=1.20 and 95% CI: 1.04-1.38 for D/D vs I/D+I/I) but not in Asians. Moderate trends of an increased risk in the D allele carriers from total sample (OR, 1.15; 95% CI: 1.02-1.30) was also observed. The D/D homozygote carriers were associated with a 28% increased risk of MDD relative to the homozygotes I/I (OR 1.28; 95% CI: 1.11-1.49). In subgroup analysis, Caucasians showed significant association (OR 1.30; 95% CI: 1.09-1.56). No association was found in the Asian groups. No publication bias was observed in this meta-analysis by using the Egger method.


The ACE I/D polymorphism is not associated with MDD and its treatment response in a Chinese case-control study. Meta-analysis evidence suggests that the I/D polymorphism of ACE gene may be a risk factor of major depressive disorder in Caucasians.

[Indexed for MEDLINE]

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