The D-allele of ACE insertion/deletion polymorphism is associated with regional white matter volume changes and cognitive impairment in remitted geriatric depression

Department of Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, PR China.
Neuroscience Letters (Impact Factor: 2.03). 08/2010; 479(3):262-6. DOI: 10.1016/j.neulet.2010.05.076
Source: PubMed


Prior studies suggested that angiotensin-converting enzyme (ACE) affected vascular homeostasis and degradation of amyloid beta (Abeta ). It is associated with the therapeutic outcome in major depression. The aim of this study was to investigate the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and structural abnormalities in remitted geriatric depression (RGD), and test the relationship of neuropsychological performances and regional white matter volumes. 31 RGD patients were recruited and neuropsychological tests, magnetic resonance imaging (MRI) and genotype of ACE I/D were examined for each subject. The differences in regional white matter volume were tested between I homozygotes and D-allele carriers (I/D or D/D genotype) by optimized VBM. D-allele carriers exhibited significantly smaller white matter volumes of right superior frontal gyrus (SFG) and right anterior cingulated gyrus (ACG), but had larger volumes of left middle temporal gyrus (MTG) and right middle occipital gyrus (MOG) than I homozygotes (P < 0.001). Meanwhile, there was a significant positive correlation between white matter volume enlargement of left MTG and Symbol Digit Modalities Test (SDMT) (r = 0.456, P = 0.043), and the reduction of right ACG was negatively related to Clock Drawing Test (CDT) performance (r = -0.445, P = 0.050) in D-allele carriers. The finding suggests that ACE can modulates the pathology of RGD, the left MTG and right ACG might be involved in the pathophysiology of cognitive dysfunction in RGD patients.

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    • "A study among elderly persons who had recovered from depression by Wu and colleagues[52] found decreased FC in the posterior cingulated cortex and temporal lobe when performing episodic memory tasks (compared to the resting-state FC) that was more pronounced among ε4 allele carriers – supporting hypotheses about the role of ApoE ε4 in brain functions related to episodic memories. Another study[53] investigating the association between angiotensin-converting enzyme (ACE) insertion/deletion polymorphisms and cognitive functioning among patients with LOD found that, compared to the I-allele, the D-allele was associated with significantly smaller volumes of white matter in the superior frontal gyrus and anterior cingulated gyrus,and with significantly larger volumes in the middle temporal gyrus and middle occipital gyrus. Moreover this study found a correlation between decline of cognitive functioning and the changes in the white matter volume in the middle temporal gyrus and the anterior cingulated gyrus. "
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    ABSTRACT: This paper reviews neuroimaging studies of depressive disorders conducted in Chinese populations since 2000. Both cross-sectional and longitudinal studies using structural and functional imaging techniques have compared different types of depressed individuals, with and without specific genotypes, and the characteristics of depressed individuals before and after treatment with antidepressants. Many of the findings are unstable - probably because most of the studies are underpowered - but there have been some important contributions to the international literature. Future studies in China need to use standardized methods, longitudinal designs, and joint application of both structural and functional MRI.
    Shanghai Archives of Psychiatry 06/2014; 26(3):113-8. DOI:10.3969/j.issn.1002-0829.2014.03.002
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    • "manufacturer's recommendations. ACE I/D genotyping was performed according to the method used in our previous study (Hou et al., 2010). "
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    ABSTRACT: 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.
    Journal of Affective Disorders 02/2012; 136(3):971-8. DOI:10.1016/j.jad.2011.08.019 · 3.38 Impact Factor
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    • "Moreover, in some studies, ε2 allele that is associated with reduced risk for AD and lower cholesterol levels predicted increased in WMH load [28], and increase in microangiopathy-related damage [29]. Variants of genes associated with control of blood pressure, such as ACE deletion [30] [31] has been linked to increased WMH burden [32] [33] [34] [35] and lacunar strokes [36]. Studies of a variant of methylenetetrahydrofolate reductase gene (MTHFR C677T) that is associated with increased plasma levels of homocysteine, a risk factor for vascular disease and AD [37] [38] [39] [42], revealed inconsistent support for its role in WMH severity [27] [40] [41]. "
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    ABSTRACT: Aging is associated with appearance of white matter hyperintensities (WMH) on MRI scans. Vascular risk and inflammation, which increase with age, may contribute to white matter deterioration and proliferation of WMH. We investigated whether circulating biomarkers and genetic variants associated with elevated vascular risk and inflammation are associated with WMH volume in healthy adults (144 volunteers, 44-77 years of age). We examined association of WMH volume with age, sex, hypertension, circulating levels of total plasma homocysteine (tHcy), cholesterol (low-density lipoprotein), and C-reactive protein (CRP), and four polymorphisms related to vascular risk and inflammation: Apolipoprotein ε (ApoE ε2,3,4), Angiotensin-Converting Enzyme insertion/deletion (ACE I/D), methylenetetrahydrofolate reductase (MTHFR) C677T, C-reactive protein (CRP)-286C>A>T, and interleukin-1β (IL-1β) C-511T. We found that larger WMH volume was associated with advanced age, hypertension, and elevated levels of homocysteine and CRP but not with low-density lipoprotein levels. Homozygotes for IL-1β-511T allele and carriers of CRP-286T allele that are associated with increased inflammatory response had larger WMH than the other allelic combinations. Carriers of the APOE ε2 allele had larger frontal WMH than ε3 homozygotes and ε4 carriers did. Thus, in healthy adults, who are free of neurological and vascular disease, genetic variants that promote inflammation and elevated levels of vascular risk biomarkers can contribute to brain abnormalities. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
    Biochimica et Biophysica Acta 08/2011; 1822(3):361-9. DOI:10.1016/j.bbadis.2011.08.007 · 4.66 Impact Factor
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