Renin–angiotensin system gene polymorphisms and colorectal cancer risk: a meta-analysis

Objective: The renin–angiotensin system gene has been implicated in the progression of colorectal cancer. Nevertheless, the details of that role remain controversial. We performed a meta-analysis to investigate the correlation between renin–angiotensin system gene polymorphisms and colorectal cancer. Methods: We retrieved relevant studies from PubMed and Embase. Subsequently, fixed or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: We identified six studies of the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism, and two studies of the angiotensinogen M235T polymorphism. The angiotensin-converting enzyme I/D polymorphism did not significantly correlate with colorectal cancer risk in the total population (DD vs. II: OR 0.77, 95% CI 0.39–1.50; DI vs. II: OR 1.05, 95% CI 0.85–1.30; dominant model: OR 0.94, 95% CI 0.68–1.31; recessive model: OR 1.01, 95% CI 0.80–1.27). Similarly, the angiotensinogen M235T polymorphism was not associated with colorectal cancer risk (TT vs. MM: OR 1.38, 95% CI 0.52–3.67; TM vs. MM: OR 1.19, 95% CI 0.96–1.47; dominant model: OR 1.28, 95% CI 0.77–2.14; recessive model: OR 1.17, 95% CI 0.53–2.59). Conclusion: Our findings suggest that the angiotensin-converting enzyme I/D and angiotensinogen M235T polymorphisms are unlikely to correlate with colorectal cancer.

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Renin–angiotensin system inhibitor use and colorectal cancer risk and mortality: A dose–response meta analysis

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320319895646 ◽

2020 ◽

Vol 21 (3) ◽

pp. 147032031989564 ◽

Cited By ~ 1

Author(s):

Xia Chen ◽

Chang-hong Yi ◽

Kuang-guan Ya

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Dose Response ◽

Meta Analysis ◽

Renin Angiotensin System ◽

Colorectal Cancer Risk ◽

Morbidity And Mortality ◽

Angiotensin System ◽

Renin Angiotensin ◽

Cancer Morbidity

Objective: This study was undertaken to determine whether use of the renin–angiotensin system (RAS) inhibitors would increase colorectal cancer morbidity and mortality. Methods: Databases were electronically searched to collect data of RAS use and colorectal cancer morbidity and mortality from inception to October 2018. Stata 12.0 software was used to perform a meta-analysis. Results: A total of 16 publications involving 2,847,597 participants were included. RAS inhibitor use was related to colorectal cancer risk (relative risk (RR): 0.86; 95% confidence interval (CI): 0.78–0.93) and mortality (RR: 0.80; 95% CI: 0.66–0.98) decrement. Subgroup analysis showed angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) (RR: 0.82; 95% CI: 0.69-0.96) or ARB (RR: 0.86; 95% CI: 0.73–0.98) or ACEI (RR: 0.81; 95% CI: 0.70–0.92) were related to colorectal cancer risk decrement. Furthermore, RAS inhibitor use was related to colorectal cancer risk decrement in Caucasians (RR: 0.88; 95% CI: 0.80–0.96) and Asians (RR: 0.72; 95% CI: 0.61–0.85). Additionally, dose–response showed that per one year duration of RAS inhibitor use incremental increase was related to 6% colorectal cancer risk decrement (RR: 0.94; 95% CI: 0.90–0.97). Conclusion: According to the evidence, RAS inhibitor use was associated with colorectal cancer risk and mortality decrement.

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Renin–angiotensin system blockers, risk of SARS-CoV-2 infection and outcomes from CoViD-19: systematic review and meta-analysis

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvaa138 ◽

2020 ◽

Author(s):

Matthew M Y Lee ◽

Kieran F Docherty ◽

Naveed Sattar ◽

Neil Mehta ◽

Ankur Kalra ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Ace Inhibitor ◽

Meta Analysis ◽

Intensive Therapy ◽

Case Fatality ◽

Renin Angiotensin System ◽

Converting Enzyme ◽

Angiotensin System ◽

Renin Angiotensin ◽

Renin Angiotensin System Blockers

Abstract Aims This meta-analysis provides summary odds ratio (OR) estimates for associations between treatment with (vs. without) renin–angiotensin system blockers and risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and coronavirus disease 2019 (CoViD-19) severity (including case-fatality) in patients with hypertension, and in all patients (irrespective of hypertension). Methods and results PubMed, EMBASE, Web of Science, Google Scholar, medRxiv, and SSRN were searched (2 May 2020 to 12 August 2020) for non-randomized observational CoViD-19 studies. Event/patient numbers were extracted, comparing angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) treatment (and each separately), to treatment with neither drug, for the outcomes: (i) likelihood of SARS-CoV-2 infection; (ii) CoViD-19 severity [including hospitalization, intensive therapy unit (ITU), ventilation]; (iii) case-fatality. The risk of bias was assessed (ROBINS-I). Random-effects meta-analysis estimates were pooled. Eighty-six studies including 459 755 patients (103 317 with hypertension), were analysed. In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60 141 patients (OR 1.06, 95% CI 0.99–1.14), hospitalization in 5925 patients (OR 0.90, 0.62–1.31), ITU in 7218 patients (OR 1.06, 0.73–1.56), ventilation (or ITU/ventilation/death) in 13 163 patients (OR 0.91, 0.72–1.15) or case-fatality in 18 735 patients with 2893 deaths (OR 0.75, 0.61–0.92). Conclusion Angiotensin-converting enzyme inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued. PROSPERO registration number CRD42020186996.

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Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽

10.1055/s-0040-1713678 ◽

2020 ◽

Vol 04 (02) ◽

pp. e138-e144 ◽

Cited By ~ 5

Author(s):

Wolfgang Miesbach

Keyword(s):

Angiotensin Ii ◽

Angiotensin Converting Enzyme ◽

Treatment Options ◽

Renin Angiotensin System ◽

Target Cells ◽

Converting Enzyme ◽

Angiotensin System ◽

Angiotensin Converting Enzyme 2 ◽

Renin Angiotensin ◽

Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

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Resveratrol ameliorates the cyclosporine-induced vascular and renal impairments: possible impact of the modulation of renin–angiotensin system

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0753 ◽

2019 ◽

Vol 97 (12) ◽

pp. 1115-1123 ◽

Cited By ~ 2

Author(s):

Seldag Bekpinar ◽

Ece Karaca ◽

Selin Yamakoğlu ◽

F. İlkay Alp-Yıldırım ◽

Vakur Olgac ◽

...

Keyword(s):

Angiotensin Ii ◽

Angiotensin Converting Enzyme ◽

Renin Angiotensin System ◽

Immunosuppressive Drug ◽

Oxidative Stress Marker ◽

Converting Enzyme ◽

Angiotensin System ◽

Renin Angiotensin ◽

System Components ◽

Renal Tubular

Cyclosporine, an immunosuppressive drug, exhibits a toxic effect on renal and vascular systems. The present study investigated whether resveratrol treatment alleviates renal and vascular injury induced by cyclosporine. Cyclosporine (25 mg/kg per day, s.c.) was given for 7 days to rats either alone or in combination with resveratrol (10 mg/kg per day, i.p.). Relaxation and contraction responses of aorta were examined. Serum levels of blood urea nitrogen, creatinine, angiotensin II, and angiotensin 1-7 were measured. Histopathological examinations as well as immunostaining for 4-hydroxynonenal and nitrotyrosine were performed in the kidney. RNA expressions of renin–angiotensin system components were also measured in renal and aortic tissues. Cyclosporine decreased the endothelium-dependent relaxation and increased vascular contraction in the aorta. It caused renal tubular degeneration and increased immunostaining for 4-hydroxynonenal, an oxidative stress marker. Cyclosporine also caused upregulations of the vasoconstrictive renin–angiotensin system components in renal (angiotensin-converting enzyme) and aortic (angiotensin II type 1 receptor) tissues. Resveratrol co-treatment prevented the cyclosporine-related deteriorations. Moreover, it induced the expressions of vasodilatory effective angiotensin-converting enzyme 2 and angiotensin II type 2 receptor in aorta and kidney, respectively. We conclude that resveratrol may be effective in preventing cyclosporine-induced renal tubular degeneration and vascular dysfunction at least in part by modulating the renin–angiotensin system.

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Effects of Yinchenhao decoction on self-regulation of renin-angiotensin system by targeting angiotensin converting enzyme 2 in bile duct-ligated rat liver

Journal of Huazhong University of Science and Technology [Medical Sciences] ◽

10.1007/s11596-015-1463-9 ◽

2015 ◽

Vol 35 (4) ◽

pp. 519-524 ◽

Cited By ~ 4

Author(s):

Lin Wu ◽

Pi-qi Zhou ◽

Ji-wen Xie ◽

Rui Zhu ◽

Sun-chang Zhou ◽

...

Keyword(s):

Bile Duct ◽

Angiotensin Converting Enzyme ◽

Rat Liver ◽

Self Regulation ◽

Renin Angiotensin System ◽

Converting Enzyme ◽

Angiotensin System ◽

Angiotensin Converting Enzyme 2 ◽

Renin Angiotensin

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Synergistic Expression of Angiotensin-Converting Enzyme (ACE) and ACE2 in Human Renal Tissue and Confounding Effects of Hypertension on the ACE to ACE2 Ratio

Endocrinology ◽

10.1210/en.2006-1287 ◽

2007 ◽

Vol 148 (5) ◽

pp. 2453-2457 ◽

Cited By ~ 68

Author(s):

Shigeyuki Wakahara ◽

Tadashi Konoshita ◽

Shinichi Mizuno ◽

Makoto Motomura ◽

Chikako Aoyama ◽

...

Keyword(s):

Renal Function ◽

Angiotensin Converting Enzyme ◽

Pairwise Comparison ◽

Renin Angiotensin System ◽

Mrna Levels ◽

Converting Enzyme ◽

Gene Expressions ◽

Angiotensin System ◽

Renin Angiotensin ◽

Clinicopathological Variables

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.

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Effect of Dual Blockade of Renin-Angiotensin System on Proteinuria

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2013.004 ◽

2013 ◽

Vol 1 (1) ◽

pp. 18-20

Author(s):

Eqerem Hasani ◽

Alma Idrizi ◽

Myftar Barbullushi

Keyword(s):

Angiotensin Converting Enzyme ◽

Angiotensin Receptor Blocker ◽

Enzyme Inhibitor ◽

Combined Therapy ◽

Renin Angiotensin System ◽

Converting Enzyme ◽

Angiotensin Receptor ◽

Angiotensin System ◽

Renin Angiotensin ◽

Dual Blockade

Aim: Aim of the study was the evaluation of the effect of dual blockade of the renin-angiotensin system (RAS) on proteinuria. Material and Methods: Sixty patients, included in the study, were treated with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker for a period of 3 months. Results: The dual blockade of RAS resulted with decrease of proteinuria, a slight increase of serum creatinine and was not associated with a lowering of blood pressure.Conclusion: Combined therapy with ACE-I and ARB results in a more complete blockade of the RAS than monotherapy. In proteinuric nephropathies it reduces significantly baseline proteinuria.

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Association of seven renin angiotensin system gene polymorphisms with restenosis in patients following coronary stenting

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320316688774 ◽

2017 ◽

Vol 18 (1) ◽

pp. 147032031668877 ◽

Cited By ~ 2

Author(s):

Min Zhu ◽

Minjun Yang ◽

Jiangbo Lin ◽

Huanhuan Zhu ◽

Yifei Lu ◽

...

Keyword(s):

Angiotensin Ii ◽

Angiotensin Converting Enzyme ◽

Neointimal Hyperplasia ◽

Renin Angiotensin System ◽

Coronary Stenting ◽

Converting Enzyme ◽

Angiotensin System ◽

Renin Angiotensin ◽

Stent Restenosis ◽

In Stent Restenosis

Background and objective: Percutaneous coronary intervention, despite being effective for coronary revascularization, causes in-stent restenosis due to neointimal hyperplasia in a large number of patients. The renin-angiotensin system is involved in neointimal hyperplasia. This study sought to evaluate seven gene polymorphisms of key renin-angiotensin system components, including angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1a receptors, and their associations with in-stent restenosis in patients with coronary artery disease following coronary stenting. Methods and results: Three hundred and fifty-two patients undergoing coronary drug-eluting stent implantation were recruited. Seventy-five patients (21.3%) were diagnosed as restenosis by angiography. Genotyping for angiotensin-converting enzyme insertion/deletion demonstrated a significant association of angiotensin-converting enzyme DD genotype with the occurrence of restenosis. Direct DNA sequencing revealed no association of angiotensinogen (M235T, G217A, G152A, G-6A, and A-20C) or angiotensin II type I receptor A1166C polymorphisms with in-stent restenosis. However, angiotensin II type 1a A1166C polymorphism was significantly associated with increased susceptibility to restenosis in a subgroup of patients aged more than 60 years. Conclusion: Thus, our study suggests that genetic polymorphisms of angiotensin-converting enzyme insertion/deletion are associated with in-stent restenosis in coronary artery disease patients following coronary stenting.

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