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Journal of Human Hypertension Aug 2016This systematic review investigates the high level of hypertension found among urban dwellers in West Africa and in the West African Diaspora in the Americas in relation... (Meta-Analysis)
Meta-Analysis Review
This systematic review investigates the high level of hypertension found among urban dwellers in West Africa and in the West African Diaspora in the Americas in relation to variants within the genes encoding the renin angiotensinogen system. For comparison, the results from the Caucasian populations are reviewed as well. Through a PubMed search, 1252 articles were identified and 28 eligible articles assessed in detail of which 13 included a Caucasian population. The results suggest that among the people of West African descent and among the people of Caucasian descent, hypertension is partly related to a number of single nucleotide polymorphisms (SNPs) and haplotypes in the renin gene, the angiotensinogen gene, the angiotensinogen I-converting enzyme gene and the angiotensinogen II type 1 receptor gene. Concordance between these two populations was found for some SNPs. However, for others, it was found that the SNPs associating with hypertension and the disease allele frequencies differed between these populations. Understanding the importance of these variants in a modern life setting may assist our understanding of the increased risk of developing hypertension among West Africans. Because of inconsistency in the results, low statistical power and methodological differences between studies, these results can only be taken as indicative of an association.
Topics: Africa, Western; Black People; Essential Hypertension; Gene Frequency; Genetic Predisposition to Disease; Humans; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Renin-Angiotensin System; Risk Assessment; Risk Factors
PubMed: 26607294
DOI: 10.1038/jhh.2015.114 -
Medicine Aug 2022It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is... (Meta-Analysis)
Meta-Analysis
The effect of polymorphisms (M235T and T174M) on the angiotensinogen gene (AGT) in coronary artery disease in the Eastern Asian population: A systematic review and meta-analysis.
BACKGROUND
It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is implicated in CAD susceptibility, but these results contradict those of the other studies with the associations being unclear in the Eastern Asian population. Therefore, meta-analysis was performed to evaluate this relationship.
METHODS
Publication databases were used to search for eligible relevant studies and valid data were extracted from studies meeting the inclusion criteria. Subsequently, odds ratios (ORs) with 95 % confidence intervals (CIs), were used to assess the strength of the association between AGT polymorphism and CAD risk.
RESULTS
Seven eligible studies published only in English were included in the present meta-analysis. In the Eastern Asian population, CAD susceptibility was shown to be related to AGT M235T under the heterozygote model (OR = 0.19). Stratified analysis indicated there was a significant relationship between AGT M235T and CAD risk in China under allelic (OR = 1.34), dominant (OR = 1.43), and heterozygote (OR = 1.62) models. The results showed that the T174M polymorphism was significantly associated with CAD risk in recessive (OR = 2.28) and homozygote (OR = 2.37) models in the Eastern Asian population.
CONCLUSIONS
In the Eastern Asian population, especially the Chinese, the M235T of AGT is associated with CAD susceptibility. The T174M polymorphisms were associated with CAD risk in the Eastern Asian population.
Topics: Angiotensinogen; Asian People; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 36042680
DOI: 10.1097/MD.0000000000029911 -
Cureus Jul 2022The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys... (Review)
Review
Effects of Renin-Angiotensin-Aldosterone System Inhibition on Left Ventricular Hypertrophy, Diastolic Function, and Functional Status in Patients With Hypertrophic Cardiomyopathy: A Systematic Review.
The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys produce renin which converts angiotensinogen to angiotensin-1 (AT-I) and angiotensin-converting enzyme (ACE) to angiotensin-II (AT-II). AT-II binds to receptors in the adrenal cortex to release aldosterone. AT-II and aldosterone promote water and salt retention, vascular tone, and myocardial contractility. These physiological changes raise blood pressure and circulation. Reduced renal perfusion pressure sensed by baroreceptors and the sympathetic nervous system's β-adrenergic receptors trigger renin release and RAAS activation. RAAS restores hemodynamic stability in pathological states associated with low perfusion. This adaptive response is important for restoring perfusion and hemodynamic stability, but prolonged RAAS activation has deleterious effects on the cardiovascular system. Long-term mineralocorticoid exposure has been linked to left ventricular hypertrophy (LVH) and remodeling. AT-II activates fibroblasts and cardiac myocytes to promote cardiac remodeling. Blocking RAAS can eliminate the long-term negative effects of RAAS activation. Direct renin inhibitors, ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists are RAAS blockers. RAAS blockade improves mortality and hospitalization in systolic heart failure and acute myocardial infarction. RAAS blockade has not demonstrated the same benefits in other cardiac populations, such as those with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) causes LVH and asymmetric septal hypertrophy. When the outflow tract gradient exceeds 30 mmHg and is associated with septal hypertrophy, it is known as obstructive HCM. Dyspnea on exertion, syncope, and exertional angina are symptoms of HCM. RAAS activation worsens LVH by increasing blood pressure and by directly affecting cardiac myocytes with AT-II and aldosterone. RAAS blockade reverses myocardial fibrosis and slows HCM progression in animal models. We performed a meta-analysis of randomized clinical trials to further investigate the potential benefit of RAAS blockade in HCM patients. Although our findings included significant results for some of the RAAS blockade agents, these findings were not consistent throughout all the studies. Mavacamten, one of the newest treatments, has shown promising outcomes.
PubMed: 35949750
DOI: 10.7759/cureus.26642 -
BMJ Open May 2019Chronic kidney disease (CKD) is defined by abnormalities in kidney structure and/or function present for more than 3 months. Worldwide, both the incidence and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic kidney disease (CKD) is defined by abnormalities in kidney structure and/or function present for more than 3 months. Worldwide, both the incidence and prevalence rates of CKD are increasing. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance through the kidney. RAAS activation is associated with hypertension, which is directly implicated in causation and progression of CKD. RAAS blockade, using drugs targeting individual RAAS mediators and receptors, has proven to be renoprotective.
OBJECTIVES
To assess genomic variants present within RAAS genes, , , , , and , for association with CKD.
DESIGN AND DATA SOURCES
A systematic review and meta-analysis of observational research was performed to evaluate the RAAS gene polymorphisms in CKD using both PubMed and Web of Science databases with publication date between the inception of each database and 31 December 2018. Eligible articles included case-control studies of a defined kidney disease and included genotype counts.
ELIGIBILITY CRITERIA
Any paper was removed from the analysis if it was not written in English or Spanish, was a non-human study, was a paediatric study, was not a case-control study, did not have a renal disease phenotype, did not include data for the genes, was a gene expression-based study or had a pharmaceutical drug focus.
RESULTS
A total of 3531 studies were identified, 114 of which met the inclusion criteria. Genetic variants reported in at least three independent publications for populations with the same ethnicity were determined and quantitative analyses performed. Three variants returned significant results in populations with different ethnicities at p<0.05: insertion, rs699-T allele and rs5186-A allele; each variant was associated with a reduced risk of CKD development.
CONCLUSIONS
Further biological pathway and functional analyses of the RAAS gene polymorphisms will help define how variation in components of the RAAS pathway contributes to CKD.
Topics: Angiotensinogen; Female; Genotype; Humans; Male; Observational Studies as Topic; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 31048445
DOI: 10.1136/bmjopen-2018-026777 -
Hypertension (Dallas, Tex. : 1979) Dec 1997Recently, an allelic variant of the angiotensinogen gene (AGT 235T) has been associated with increased risk of hypertension. However, this finding has not been confirmed... (Review)
Review
Recently, an allelic variant of the angiotensinogen gene (AGT 235T) has been associated with increased risk of hypertension. However, this finding has not been confirmed by all investigators. A meta-analysis was performed to examine the association between the AGT 235T-allele and hypertension in whites and to identify potential reasons for the controversial results. All relevant articles published between 1992 and 1996 were identified through multiple sources. The studies were methodologically appraised, and the frequency of the AGT 235T-allele was extracted. The 235T-allele frequency was pooled using the common odds ratio (OR) estimator by Mantel-Haenszel. Homogeneity was assessed using the Breslow-Day test. Together these studies present data on 5493 patients. The AGT 235T-allele was significantly associated with hypertension (OR: 1.20; 95% [CI]: 1.11 to 1.29; P<.0001). This association increased in studies with positive family history (OR: 1.42; 95% CI: 1.25 to 1.61, P<.0001), recruitment of cases from referral centers (OR: 1.39; 95% CI: 1.20 to 1.62, P<.0001), and more severe hypertension (OR: 1.34; 95% CI: 1.22 to 1.47, P<.0001). However, the presence of methodological problems in all studies gives rise to serious concerns regarding bias and confounding. Despite a statistically significant, albeit weak, association between the AGT 235T variant and hypertension that has been confirmed through sensitivity analysis, this finding has to be interpreted with caution, as the methodological weaknesses of the individual studies are likely to have biased the outcome of the meta-analysis. Clearly, more rigorous methods need to be applied in association studies on the genetics of human hypertension.
Topics: Alleles; Angiotensinogen; Biometry; Databases, Bibliographic; Gene Frequency; Genetic Variation; Humans; Hypertension; MEDLINE; Odds Ratio; Sensitivity and Specificity; White People
PubMed: 9403549
DOI: 10.1161/01.hyp.30.6.1331 -
Journal of Research in Medical Sciences... Nov 2014The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of... (Review)
Review
BACKGROUND
The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM) and its complications of retinopathy, neuropathy and cardiovascular disease (CVD).
MATERIALS AND METHODS
The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM), T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR), diabetic neuropathy and cardiovascular complication of DM.
RESULTS
The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT) M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor gene (AT1R) A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients.
CONCLUSION
More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications.
PubMed: 25657757
DOI: No ID Found -
Progres En Urologie : Journal de... Feb 2014A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the... (Review)
Review
INTRODUCTION
A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers.
MATERIAL AND METHOD
We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting.
RESULTS
Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers.
CONCLUSION
Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings.
Topics: Humans; Renin-Angiotensin System; Urologic Neoplasms
PubMed: 24485075
DOI: 10.1016/j.purol.2013.09.010 -
Anatolian Journal of Cardiology Mar 2019M235T polymorphism of the angiotensinogen (AGT) gene has been linked with cardiovascular disease (CVD). The aim of this meta-analysis was to investigate whether combined... (Meta-Analysis)
Meta-Analysis
OBJECTIVE:
M235T polymorphism of the angiotensinogen (AGT) gene has been linked with cardiovascular disease (CVD). The aim of this meta-analysis was to investigate whether combined evidence supports this association.
METHODS:
A systematic search was conducted for studies published up to October 2018 that evaluate the association between AGT M235T polymorphism and risk of CVD. Case–control studies were identified, and the association between AGT M235T polymorphism and CVD risk was assessed using genetic models.
RESULTS:
Thirty-nine comparisons from 38 studies were collected, and a meta-analysis and subgroup analysis was performed based on ethnicity. In the overall population (9225 cases and 8406 controls), the occurrence of CVD was found to be associated with AGT M235T polymorphism in both allelic [T vs. M: odds ratio (OR)=1.16] and recessive (TT vs. MT+MM: OR=1.14) models. In subgroup analyses, a significant association was identified between AGT M235T polymorphism and CVD risk in East Asian subgroups in allelic (T vs. M: OR=1.46), homozygous (TT vs. MM: OR=1.78), dominant (MT+TT vs. MM: OR=1.47), and recessive (TT vs. MT+ MM: OR=1.68) models, but there was no significant association in Caucasian populations.
CONCLUSION:
Among East Asians, the AGT variant M235T is associated with CVD risk. However, current evidence suggests that there is no such association in the Caucasian population.
Topics: Angiotensinogen; Asian People; Cardiovascular Diseases; Case-Control Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic
PubMed: 30930452
DOI: 10.14744/AnatolJCardiol.2019.75282 -
Journal of Hypertension Jul 2004To assess the role of genetic polymorphisms in salt sensitivity of blood pressure. (Review)
Review
PURPOSE
To assess the role of genetic polymorphisms in salt sensitivity of blood pressure.
DATA IDENTIFICATION
We conducted a systematic review by searching the Medline literature from March 1993 to June 2003. Each paper was scrutinized and data concerning study population, method of salt sensitivity testing, blood pressure measurement, definition of salt sensitivity, and effects were extracted.
STUDY SELECTION AND DATA EXTRACTION
A total of 23 studies met the inclusion criteria. There was considerable heterogeneity in the method of salt sensitivity testing among the studies. Due to these differences, it was impossible to perform pooled analyses by genetic variants. Detailed investigation was done on the alpha-adducin Gly460Trp, ACE I/D, angiotensinogen M235T, G protein beta 3 C825T, aldosterone synthase gene and 11 beta-hydroxysteroid dehydrogenase type 2 G534A polymorphism.
RESULTS AND CONCLUSIONS
Our analysis shows that the 460Trp variant of the alpha-adducin polymorphism is probably associated with a sodium-sensitive form of hypertension, while the polymorphisms of the angiotensin II type 1 receptor gene and the -344C/T variant of the aldosterone synthase gene are not associated with this phenotype. In view of the lack of standardization in salt sensitivity testing, we propose uniformity in study design in these type of studies.
Topics: Genetic Predisposition to Disease; Humans; Hypertension; Polymorphism, Genetic; Sodium Chloride
PubMed: 15201536
DOI: 10.1097/01.hjh.0000125443.28861.0d -
Pediatric Nephrology (Berlin, Germany) Oct 2021Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved...
BACKGROUND
Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N).
OBJECTIVE
The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity.
METHODS
A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values.
RESULTS
One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-β-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity.
CONCLUSIONS
Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.
Topics: Area Under Curve; Biomarkers; Child; Humans; IgA Vasculitis; Immunoglobulin A; Kidney Failure, Chronic; Male; Nephritis
PubMed: 33993342
DOI: 10.1007/s00467-021-05107-7