Increased amount of the angiotensin-converting enzyme (ACE) mRNA originating from the ACE allele with deletion

Suehiro, Tadashi; Morita, Tatsuhito; Inoue, Mari; Kumon, Yoshitaka; Ikeda, Yukio; Hashimoto, Kozo

doi:10.1007/s00439-004-1136-4

Cited by 72 publications

(56 citation statements)

References 25 publications

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“…The serum and tissue expression, and hence the activity of ACE, is influenced by the insertion/deletion gene polymorphism, with an increased amount of ACE mRNA originating from the D allele (30). Recently, several studies have investigated the influence of this I/D gene polymorphism on cancer risk (15, 31 -34) (33) found a significant link between the occurrence of the DD ACE gene polymorphism and the incidence of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

Röcken

Lendeckel²,

Dierkes³

et al. 2005

Clinical Cancer Research

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Purpose: In the present study, we aimed to substantiate the putative significance of angiotensin I^converting enzyme (ACE) on gastric cancer biology by investigating the influence of its gene polymorphism on gastric cancer progression. Experimental Design: Genomic DNA was purified from peripheral blood mononuclear cells or tissue specimens. Amplified ACE gene fragments were separated on agarose gels. D or I alleles were identified by the presence of 190-or 490-bp fragments, respectively. Local expression of ACE was investigated by immunohistochemistry. Results: Twenty-four of 113 (21%) gastric cancer patients had the II, 57 (51%) the ID, and 32 (28%) the DD genotype. The distribution of the ACE genotypes did not differ significantly from the control group of 189 patients without gastric cancer. However, the ACE genotypes correlated with the number of lymph node metastases and the Unio Internationale Contra Cancrum (UICC) tumor stage. Patients with the II genotype had a highly significantly smaller number of lymph node metastases (P < 0.001) and a significantly lower UICC tumor stage (P = 0.01) than patients with the DD genotype. No correlation was found between tumor type, tumor location, local tumor growth, distant metastases, and the ACE genotype. The expression of ACE in gastric cancer was investigated by immunohistochemistry in 100 of 113 patients. ACE was expressed by endothelial cells in all (100%) specimens and by tumor cells in 56 (56%) specimens. Conclusions: Our study shows that ACE is expressed locally in gastric cancer and that the gene polymorphism influences metastatic behavior.

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Section: Discussionmentioning

confidence: 99%

The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

Röcken

Lendeckel²,

Dierkes³

et al. 2005

Clinical Cancer Research

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“…The ACE I/D polymorphism is strongly associated with plasma and cellular ACE levels, and it indicates that the polymorphism may modulate the expression of the ACE gene. 11,38 Many studies found that DD genotypes and the D allele of the ACE gene were strongly associated with hypertension in different populations. [39][40][41][42][43][44][45][46] Hypertension is an important cause of ganglionic, pontine, cerebellar and lobar hemorrhages and can as well be the cause of lobar hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: A meta-analysis of epidemiologic studies

Huang¹,

Li²,

Lan³

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Studies investigating the association between the intron 16 insertion/deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) gene and risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratios (OR) and 95% confidence limits (CLs) were calculated in fixed-or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 744 ICH cases and 1411 controls. The combined results based on all studies showed that ICH cases had a significantly lower frequency of ID genotype (OR (codominant model) = 0.43, 95% CL = 0.22, 0.84, p = 0.01). In the subgroup analysis by race, we found that ICH cases had a significantly lower frequency of II genotype in Asians (OR (recessive model) = 0.50, 95% CL = 0.38, 0.66, p < 0.001; OR (codominant model) = 0.25, 95% CL = 0.09, 0.71, p = 0.009). In conclusion, our meta-analysis suggests that ACE I/D polymorphisms are associated with ICH, especially in Asians.

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“…It has been considered as a functional variant, since the ACE DD genotype was associated with higher circulating [124][125][126] and tissue mRNA levels of ACE [127,128]. Among 78 variations that were found by ACE gene sequencing, 17 were in absolute linkage disequilibrium with the I/D polymorphism [129].…”

Section: Main Ras Molecules In Atherosclerosis Through the Magnifyingmentioning

confidence: 99%

Involvement of the Renin‐Angiotensin System in Atherosclerosis

Kolaković¹,

Živković²,

Stanković³

2017

Renin-Angiotensin System - Past, Present and Future

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The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).

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Increased amount of the angiotensin-converting enzyme (ACE) mRNA originating from the ACE allele with deletion

Cited by 72 publications

References 25 publications

The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: A meta-analysis of epidemiologic studies

Involvement of the Renin‐Angiotensin System in Atherosclerosis

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