RESUMEN

Alamandine is a peptide hormone belonging to the renin-angiotensin system (RAS). It acts through the Mas-related G-protein coupled receptor type D, MrgD, which is expressed in different tissues, including the brain. In the present study, we hypothesize that a lack of alamandine, through MrgD, could cause the anxiety-like behavior in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)680]. Adult male transgenic rats exhibited a significant increase in the latency to feeding time in the novelty suppressed feeding test and a decrease in the percentage of time and entries in the open arms in the elevated plus maze. These effects were reversed by intracerebroventricular infusion of alamandine. Pretreatment with D-Pro7-Ang-(1-7), a Mas and MrgD receptor antagonist, prevented the anxiolytic effects induced by this peptide. However, its effects were not altered by the selective Mas receptor antagonist, A779. In conclusion, our data indicates that alamandine, through MrgD, attenuates anxiety-like behavior in male TGR(ASrAOGEN)680, which reinforces the importance of the counter-regulatory RAS axis as promising target for the treatment of neuropsychiatric disorders.

Asunto(s)

Angiotensinógeno , Ansiolíticos , Ansiedad , Encéfalo , Ratas Transgénicas , Receptores Acoplados a Proteínas G , Animales , Masculino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ratas , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Ansiolíticos/farmacología , Angiotensinógeno/metabolismo , Angiotensinógeno/genética , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Receptores de la Hormona Gastrointestinal/metabolismo , Oligopéptidos/farmacología , Proteínas del Tejido Nervioso

RESUMEN

Background: Essential hypertension is the result of modifiable and genetic factors, and it is associated with increased risk for atherothrombosis. Some polymorphisms are associated with hypertensive disease. The objective was to analyze the association between eNOS Glu298Asp, MTHR C677T, AGT M235T, AGT T174M, and A1166C and ACE I/D polymorphisms with essential hypertension in the Mexican population. Materials and Methods: In the present study, 224 patients with essential hypertension and 208 subjects without hypertension were included. The Glu298Asp, C677T, M235T, T174M, A1166C, and I/D polymorphisms were determined by the PCR-RFLP technique. Results: We found statistical differences in age, gender, BMI, systolic and diastolic blood pressure, and total cholesterol between control and cases. However, we found no significant differences in HbA1c and triglycerides between both groups. We observed statistical significant differences in the genotype distribution of Glu298Asp (P = 0.001), I/D (P = 0.02), and M235T (P = 0.004) polymorphisms between both groups. In contrast, there were no differences related to distribution of genotypes of MTHFR C677T (P = 0.12), M174T (P = 0.46), and A1166C (P = 0.85) between cases and control groups. Conclusions: We identified that Glu298Asp, I/D, and M234T polymorphisms represented an increased risk for essential hypertension and those genetic variants could contribute to the presence of endothelial dysfunction and vasopressor effect, hyperplasia, and hypertrophy of smooth muscle cells, which had an impact for hypertension. In contrast, we found no association between C677C, M174T, and A1166C polymorphisms and hypertensive disease. We suggested that those genetic variants could be identified in individuals with high risk to avoid hypertension and thrombotic disease.

Asunto(s)

Hipertensión , Sistema Renina-Angiotensina , Humanos , Angiotensinógeno/genética , Hipertensión Esencial/genética , Genotipo , Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Sistema Renina-Angiotensina/genética

RESUMEN

AIMS: Since angiotensinogen has a pivotal role in the renin-angiotensin-aldosterone system, the analysis of polymorphisms of the angiotensinogen (AGT) gene could help explain its potential involvement in hypertension and diabetic nephropathy (DN) pathogenesis. For that reason, we investigated 1) the association of AGT rs4762 with blood pressure (BP) and kidney function-related traits and 2) the interaction effect of AGT rs4762 with DN on BP and kidney function-related traits in 546 Mexican adults with type 2 diabetes (T2D). METHODS: We enrolled 546 unrelated Mexican patients with T2D (350 cases with DN and 196 controls without DN). AGT rs4762 was genotyped in all participants using TaqMan technology (effect allele: A). BP and kidney function-related traits, including serum urea and creatinine, urinary albumin, urine albumin to urine creatinine ratio (ACR), and glomerular filtration rate, were studied. DN was defined as having a previous diagnosis of T2D and an ACR ≥ 30 mg/g. The association between these parameters was investigated using logistic regression with adjustment for covariates. RESULTS: AGT rs4762 A allele was significantly associated with diastolic blood pressure (N = 546, ß = 1.243 ± 0.918, p = 0.029). A significant interaction between DN and AGT rs4762 was also observed in relation to diastolic blood pressure (DBP) (N = 546, ß = 0.930 ± 0.433, p=0.032). A follow-up analysis of simple effects particularly revealed a positive association between AGT rs4762 A allele and DBP only in patients with diabetic nephropathy (N = 350, ß = 2.837 ±â€¯1.267, p = 0.026). CONCLUSION: Our results evidence that, although AGT rs4762 is not associated with DN, the AGT rs4762 A allele is positively associated with DBP in the Mexican population with DN.

Asunto(s)

Angiotensinógeno , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Adulto , Albúminas , Angiotensinógeno/genética , Presión Sanguínea , Creatinina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/genética , Humanos , México , Sistema Renina-Angiotensina/genética

RESUMEN

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Asunto(s)

Angiotensinógeno/genética , Astrocitoma/genética , Neoplasias Encefálicas/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Variación Genética/genética , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/genética , Adulto , Astrocitoma/epidemiología , Astrocitoma/patología , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/patología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad

RESUMEN

Functional variants in genes of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems have already been implicated in blood pressure (BP) modulation, but few studies have focused on a nutrigenetics approach. Thus, the aim of this study is to verify the effects of the interaction between genetic polymorphisms (rs4340-ACE, rs699-AGT, and rs1799722-BDKRB2) and micronutrient consumption (sodium, potassium, calcium, and magnesium) on BP values of normotensive adult individuals. The study included 335 adults, men and women, 25.5 (6.6) years old. Biochemical, anthropometric, BP measurements, and food intake data were assessed for all participants. Gene-nutrient interaction on BP outcome was tested by multiple linear regression with manual backward stepwise modeling. Our results indicated that individuals with G allele for rs699 polymorphism, in the increase of sodium and magnesium consumption, both in the genotypic model (sodium, p = 0.035; magnesium, p = 0.016) and in the dominant model (sodium, p = 0.009; magnesium, p = 0.006) had higher systolic BP (SBP) levels compared to AA homozygotes (sodium, p = 0.001; magnesium, p < 0.001). Also, individuals with the T allele for the rs1799722 polymorphism, with higher calcium intake, had significantly higher levels of SBP and diastolic BP (DBP) when compared to CC homozygotes (p = 0.037). In conclusion, our findings pointed for significant interactions between genetic polymorphisms (rs699-AGT and rs1799722-BDKRB2) and the consumption of micronutrients (sodium, magnesium, and calcium) on the BP variation. These findings contribute to the understanding of the complex mechanisms involved in BP regulation, which probable include several gene-nutrition interactions.

Asunto(s)

Angiotensinógeno/genética , Presión Sanguínea , Dieta , Hipertensión/fisiopatología , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Receptor de Bradiquinina B2/genética , Adulto , Calcio/administración & dosificación , Estudios Transversales , Femenino , Humanos , Hipertensión/genética , Magnesio/administración & dosificación , Masculino , Potasio/administración & dosificación , Sodio/administración & dosificación

RESUMEN

Alamandine (Ala1-Arg2-Val3-Tyr4-Ile5-His6-Pro7), a heptapeptide hormone of the renin-angiotensin system (RAS), exerts its effects through the Mas-related G-protein coupled receptor of the type D, MrgD, which is expressed in different tissues, including the brain. In the present study, we tested the hypothesis that alamandine could attenuate the depression-like behavior observed in transgenic rats with low brain angiotensinogen, TGR (ASrAOGEN)680. Transgenic rats exhibited a significant increase in the immobility time in forced swim test, a phenotype reversed by intracerebroventricular infusion of alamandine. Pretreatment with D-Pro7-Ang-(1-7), a Mas/MrgD receptor antagonist, prevented the antidepressant-like effect induced by this peptide demonstrating, for the first time, that alamandine through MrgD receptor, can modulate depression-like behavior in TGR (ASrAOGEN)680. This result shows an action of alamandine which strengthens the importance of the counter-regulatory arms of the RAS in fight and treatment of neuropsychiatric diseases.

Asunto(s)

Angiotensinógeno/genética , Antidepresivos/farmacología , Encéfalo/efectos de los fármacos , Proteínas del Tejido Nervioso/fisiología , Oligopéptidos/farmacología , Receptores Acoplados a Proteínas G/fisiología , Angiotensina I/farmacología , Angiotensinógeno/metabolismo , Animales , Encéfalo/metabolismo , Inyecciones Intraventriculares , Masculino , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Oligopéptidos/administración & dosificación , Fragmentos de Péptidos/farmacología , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/metabolismo

RESUMEN

Pathologies linked to the renin-angiotensin system are frequent, and the drugs used in them are numerous and show great variability in therapeutic effects and adverse reactions. Genetic variants have been detected in the angiotensinogen gene (6), angiotensin-converting enzyme (9), angiotensinconverting enzyme 2 (1), and angiotensin receptor Type 1 (4) among others. However, the large number of studies that have analyzed each of them makes it complex and almost impossible to consider all the existing information. This manuscript aims to review the effects of the different known variants on the expected response of different drugs as a basis for the future development of therapeutic guidelines that seek to implement therapeutic individualization strategies on the renin-angiotensin system.

Asunto(s)

Medicina de Precisión/métodos , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Aminopeptidasas/genética , Enzima Convertidora de Angiotensina 2/genética , Angiotensinógeno/genética , Animales , Humanos , Peptidil-Dipeptidasa A/genética , Receptor de Angiotensina Tipo 1/genética

RESUMEN

OBJECTIVE: The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. SUBJECTS AND METHODS: The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. RESULTS: The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). CONCLUSIONS: We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

Asunto(s)

Obesidad/genética , Sobrepeso/genética , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Adulto , Distribución por Edad , Angiotensinógeno/genética , Presión Sanguínea , Índice de Masa Corporal , Brasil , Estudios Transversales , Femenino , Frecuencia de los Genes/genética , Humanos , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/genética , Distribución por Sexo , Circunferencia de la Cintura

RESUMEN

ABSTRACT Objective The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. Subjects and methods The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. Results The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). Conclusions We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Sobrepeso/genética , Obesidad/genética , Presión Sanguínea , Brasil , Índice de Masa Corporal , Angiotensinógeno/genética , Estudios Transversales , Distribución por Sexo , Distribución por Edad , Peptidil-Dipeptidasa A/genética , Circunferencia de la Cintura , Frecuencia de los Genes/genética

RESUMEN

OBJECTIVE: The renin-angiotensin system (RAS) is a hormonal signaling mechanism implicated in the atherosclerosis and regulation of blood pressure. Angiotensin-converting enzyme (ACE) a key enzyme in the RAS, plays important roles in vascular remodeling atherosclerosis, and ischemic stroke. The aim of this study was to examine the possible contribution of the I/D in the ACE gene, M235T and T174M in the angiotensinogen (AGT) gene polymorphisms with ischemic stroke in young Mexican population. MATERIALS AND METHODS: A total of 224 patients with diagnosis of idiopathic ischemic stroke ≤45 years of age, and 224 controls matched by age and gender, were recruited from 2006 and 2016. The I/D, M235T and T174M polymorphisms were determined in all participants by PCR-RFLP. RESULTS: There was a significant difference in the M235T genotype distribution (p = 0.01) and allele frequency between two groups (p = 0.01). Also, we found a significant difference in the T174M genotype distribution (p = 0.01) and the allele frequency between groups; (p = 0.02). In contrast, in I/D polymorphism, there was a similar genotype distribution; (p = 0.20) and allele distribution (p = 0.20). There were independent factors for ischemic stroke: M235T and T174M polymorphisms, smoking, hypertension, and familial history of atherothrombotic disease. The AGT levels were increased in the group of patients with stroke compared with the control group, but the AGT levels were not influenced by the allele or genotype in each polymorphism. CONCLUSIONS: The M235T and T174M polymorphisms represented an increased risk for stroke in young Mexican individuals. In contrast, the I/D was not associated with in the same group of patients. The AGT levels were higher in the acute phase of stroke, but it was not determined by the polymorphisms.

Asunto(s)

Angiotensinógeno/genética , Isquemia Encefálica/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Accidente Cerebrovascular/genética , Adulto , Alelos , Presión Sanguínea/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Hipertensión/genética , Masculino , México , Polimorfismo de Longitud del Fragmento de Restricción/genética , Sistema Renina-Angiotensina/genética , Factores de Riesgo

RESUMEN

: The renin-angiotensin system plays an important role in the regulation of blood pressure and the development of coronary artery disease. The aim was to examine the association of the insertion deletion in the angiotensin-converting enzyme gene, M235T and T174M polymorphisms in the angiotensinogen gene with ST elevation acute myocardial infarction (STEAMI) in young Mexican population. We analyzed 242 unrelated patients with STEAMI 45 or less years of age, admitted to a cardiovascular intense care unit, and 242 individuals without STEAMI matched by age and sex, recruited from January 2006 and June 2013. The polymorphisms insertion deletion, M235T and T174M were determined in all participants by a polymerase chain-reaction-restriction fragment length polymorphism assay. There was a significant difference in the insertion deletion genotype distribution between two groups (P = 0.03) and a higher percentage of the T allele M235T polymorphism in the group of STEAMI patients (P = 0.02). The T174M polymorphism was not associated (P = 0.08). The insertion deletion and M235T polymorphisms, smoking, hypertension, familial history of cardiovascular disease and dyslipidemia were independent risk factors for STEAMI. Our results identified that the D allele from the insertion deletion and M235T but not T174M polymorphisms represent an independent risk factor for STEAMI in young Mexican population.

Asunto(s)

Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Infarto del Miocardio con Elevación del ST/etiología , Adulto , Angiotensinógeno/genética , Humanos , México , Persona de Mediana Edad , Riesgo , Factores de Riesgo , Adulto Joven

RESUMEN

This study investigated whether ACTN3 R577X, AMPD1 C34T, I/D ACE, and M235T AGT polymorphisms can affect performance tests such as jumping, sprinting, and endurance in 220 young male athletes from professional minor league soccer team from São Paulo Futebol Clube, Brazil. I/D ACE and M235T AGT polymorphisms were also analyzed according to cardiac and hemodynamic parameters. Athletes were grouped or not by age. DNA from saliva and Taqman assays were used for genotyping 220 athletes and the results were associated with performance tests. Ventricle mass, ventricle end-diastolic diameter, end-diastolic volume, and ejection fraction were assessed by echocardiogram. Arterial pressure, heart rate, and oximetry were assessed by a cardioscope. The main results of this study were that athletes who carried RR/RX (ACTN3) and DD (ACE) genotypes presented better performance during jump and sprint tests. On the other hand, athletes with ID/II genotype presented better results during endurance test, while AGT genotypes did not seem to favor the athletes during the evaluated physical tests. CC genotype (AMPD1) only favored the athletes during 10-m sprint test. Although there are environmental interactions influencing performance, the present results suggest that RR/RX ACTN3 and ACE DD genotypes may benefit athletes in activities that require strength and speed, while II ACE genotype may benefit athletes in endurance activities. This information could help coaches to plan the training session to improve the athletes' performance.

Asunto(s)

Rendimiento Atlético , Hemodinámica , Polimorfismo Genético , Fútbol , AMP Desaminasa/genética , Actinina/genética , Adolescente , Adulto , Angiotensinógeno/genética , Atletas , Brasil , Técnicas de Genotipaje , Humanos , Estilo de Vida , Masculino , Peptidil-Dipeptidasa A/genética , Análisis de Secuencia de ADN , Adulto Joven

RESUMEN

ABSTRACT Objective Metabolic syndrome (MetS) is associated with hypertension, obesity and dyslipidemia. Thus, genetic variants related with these conditions may modulate its development. We evaluated the effect of polymorphisms in the renin-angiotensin system (RAS) on metabolic syndrome risk in a cohort of Chilean subjects. Subjects and methods A total of 152 subjects, 83 with MetS (51.2 ± 9.6 years) and 69 without MetS (49.5 ± 9.3 years) of both genders were included, according to the ATP III update criteria. The rs4340 Insertion/Deletion (I/D), rs699 (T>C) and rs5186 (A>C) of the ACE, AGT and AGTR1 genes, respectively, were genotyped. Results After adjusting for age and gender, we observed the DD genotype of rs4340 associated with MetS (p = 0.02). Specifically, the DD genotype was associated with MetS risk in women (OR = 4.62, 95%CI, 1.41 – 15.04; p < 0.01). In males, the AA genotype for rs5186 variant was associated with an increased risk for developing MetS when compared with women carrying the same genotype (OR = 3.2; 95%CI, 1.03 – 9.89; p = 0.04). In subjects without MetS, DD genotype was associated with increased waist circumference (p = 0.023) while subjects with MetS carrying the rs5186 TT genotype showed higher levels of HDL-cholesterol (p = 0.031). Conclusion The present study contributes data highlighting the role for RAS polymorphisms in predisposing to metabolic syndrome in Chilean subjects.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Síndrome Metabólico/genética , Hipertensión/genética , Chile , Factores Sexuales , Angiotensinógeno/genética , Estudios Transversales , Estudios de Cohortes , Factores de Edad , Eliminación de Gen , Peptidil-Dipeptidasa A/genética , Predisposición Genética a la Enfermedad , Receptor de Angiotensina Tipo 1/genética , Genotipo

RESUMEN

The rennin-angiotensin-aldosterone system (RAAS) is a critical pathway in regulating blood pressure and salt/water homeostasis, possessing an intimate relationship with the development of systemic artery hypertension (SAH). Once hypertension is considered a risk factor for coronary artery disease (CAD), the RAAS is also related to this pathology. This investigation aimed to analyse if the frequencies of AGT M235T (rs699) and ACE I/D (rs4646994) polymorphisms are associated with CAD and SAH in African-Brazilians and Caucasian-Brazilians. In this study we analysed 714 subjects who underwent coronary angiography to detect obstructive lesions and CAD, as well as blood pressure measurement and SAH, grouped according to ethnicity: 266 African-Brazilians and 448 Caucasian-Brazilians. Among CAD and SAH cases and controls, the genotype and allele frequencies of ACE I/D polymorphism were similar in both ethnic groups. The AGT 235TT genotype and 235T allele frequencies were higher in SAH cases (32%, 54.7%) versus controls in Caucasian-Brazilians (19.8%, 46.4%; P = 0.038, P = 0.031, respectively). The AGT 235TT (OR = 1.8; P = 0.028) demonstrated to be an independent factor risk in a multivariate logistic regression increasing SAH risk in Caucasians but not in African-Brazilians. In summary, AGT M235T polymorphism was associated with SAH risk in Caucasian-Brazilians, and no association was detected with CAD. No association was also observed in ACE I/D polymorphism either in CAD or SAH in African-Brazilians and Caucasian-Brazilians.

Asunto(s)

Angiotensinógeno/genética , Población Negra/genética , Enfermedad de la Arteria Coronaria/genética , Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Población Blanca/genética , Adulto , Brasil , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVE: Metabolic syndrome (MetS) is associated with hypertension, obesity and dyslipidemia. Thus, genetic variants related with these conditions may modulate its development. We evaluated the effect of polymorphisms in the renin-angiotensin system (RAS) on metabolic syndrome risk in a cohort of Chilean subjects. SUBJECTS AND METHODS: A total of 152 subjects, 83 with MetS (51.2 ± 9.6 years) and 69 without MetS (49.5 ± 9.3 years) of both genders were included, according to the ATP III update criteria. The rs4340 Insertion/Deletion (I/D), rs699 (T>C) and rs5186 (A>C) of the ACE, AGT and AGTR1 genes, respectively, were genotyped. RESULTS: After adjusting for age and gender, we observed the DD genotype of rs4340 associated with MetS (p = 0.02). Specifically, the DD genotype was associated with MetS risk in women (OR = 4.62, 95%CI, 1.41 - 15.04; p < 0.01). In males, the AA genotype for rs5186 variant was associated with an increased risk for developing MetS when compared with women carrying the same genotype (OR = 3.2; 95%CI, 1.03 - 9.89; p = 0.04). In subjects without MetS, DD genotype was associated with increased waist circumference (p = 0.023) while subjects with MetS carrying the rs5186 TT genotype showed higher levels of HDL-cholesterol (p = 0.031). CONCLUSION: The present study contributes data highlighting the role for RAS polymorphisms in predisposing to metabolic syndrome in Chilean subjects.

Asunto(s)

Hipertensión/genética , Síndrome Metabólico/genética , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Adulto , Factores de Edad , Anciano , Angiotensinógeno/genética , Chile , Estudios de Cohortes , Estudios Transversales , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/genética , Receptor de Angiotensina Tipo 1/genética , Factores Sexuales

RESUMEN

The A-20C polymorphism in the angiotensinogen (AGT) gene has been associated with increased risk of essential hypertension in several studies; however, these studies gave inconsistent results. In this study, we performed a meta-analysis to assess the association between AGT A-20C polymorphism and essential hypertension. Published literature was retrieved from PubMed. Pooled odd's ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effect models. A total of 10 case-control studies containing 3653 cases and 3457 controls were enrolled to this meta-analysis. In a combined analysis, the results showed a significant association between the AGT A-20C polymorphism and risk of essential hypertension (AA vs CC: OR = 0.62, 95%CI = 0.46-0.84; recessive model: OR = 0.66, 95%CI = 0.49-0.88). In the subgroup analysis stratified by race, significant associations were found between the AGT A-20C polymorphism and essential hypertension risk in Asians (AA vs CC: OR = 0.59, 95%CI = 0.43-0.80; recessive model: OR = 0.63, 95%CI = 0.46-0.85). In conclusion, the results of this meta-analysis suggested that the AGT A-20C polymorphism was associated with risk of essential hypertension in Asians.

Asunto(s)

Angiotensinógeno/genética , Hipertensión/genética , Polimorfismo de Nucleótido Simple/genética , Pueblo Asiatico , Hipertensión Esencial , Predisposición Genética a la Enfermedad/genética , Humanos , Oportunidad Relativa

RESUMEN

Numerous studies have evaluated the association between the angiotensinogen (AGT) G-217A gene polymorphism and essential hypertension risk. However, the results have been inconsistent. We examined whether the AGT G-217A gene polymorphism confers essential hypertension risk by conducting a meta-analysis. We conducted a literature search of the Google Scholar, PubMed, and China National Knowledge Infrastructure databases for relevant studies that examined the G-217A polymorphism and risk of essential hypertension. Statistical analyses were carried out using Stata 12.0 to combine all relevant studies. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the strength of this association. A total of 2017 patients with psoriasis and 1708 controls from 7 comparative studies were included in this meta-analysis. We found a significant association between the AGT G-217A gene polymorphism and the risk of essential hypertension (AA vs GG: OR = 2.52, 95%CI = 1.68-3.78; AA vs GA: OR = 2.26, 95%CI = 1.48-3.45; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.20, 95%CI = 1.03-1.39). Further stratified analyses were conducted by ethnicity and sample size and produced similar results. No evidence of publication bias was found. This meta-analysis confirms that the AGT G-217A gene polymorphism is associated with essential hypertension susceptibility.

Asunto(s)

Angiotensinógeno/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Hipertensión/genética , Hipertensión Esencial , Humanos , Hipertensión/patología , Polimorfismo de Nucleótido Simple , Factores de Riesgo

RESUMEN

The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as susceptibility markers for coronary artery disease (CAD) and/or restenosis after coronary stent placement in a group of Mexican patients. Five polymorphisms of the AGT (rs699, rs4762, rs5051, rs5049, rs5046) and two of the REN (rs5707, rs5705) genes were analyzed by 5' exonuclease TaqMan genotyping assays in 240 patients with CAD who underwent coronary artery stenting (76 with restenosis and 164 without restenosis). A group of 610 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. The results showed that the distribution of AGT and REN polymorphisms were similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant, heterozygous and additive models, the REN A4280C (rs5705) polymorphism was associated with increased risk of CAD (OR=1.76, PCo-dom=0.006, OR=1.81, PDom=0.001, OR=1.75, PHet=0.003 and OR=1.59, PAdd=0.003, respectively). All models were adjusted for age, gender, diabetes, dyslipidemia, hypertension and smoking habit. The TC haplotype of the REN gene was associated with increased risk of CAD (OR=1.53, P=0.014). The data suggest that the REN C4280A (rs5705) polymorphism plays an important role in the risk of developing CAD with the highest risk for C allele, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Asunto(s)

Enfermedad de la Arteria Coronaria/genética , Polimorfismo de Nucleótido Simple , Renina/genética , Anciano , Alelos , Angiotensinógeno/genética , Angiotensinógeno/metabolismo , Estudios de Casos y Controles , Biología Computacional , Reestenosis Coronaria/genética , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Técnicas de Genotipaje , Haplotipos , Heterocigoto , Humanos , Desequilibrio de Ligamiento , Modelos Logísticos , Masculino , México , Persona de Mediana Edad , Renina/metabolismo , Factores de Riesgo , Stents

RESUMEN

Numerous studies have evaluated the association between the T174M polymorphism in the angiotensinogen (AGT) gene and myocardial infarction (MI) risk. However, the specific association remains controversial because of small sample sizes and varied study designs among different studies. We performed a meta-analysis to assess this correlation. A comprehensive search was conducted to identify all published articles regarding the association between the AGT gene T174M polymorphism and MI risk from different databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and heterogeneity and publication bias were assessed. A total of 1032 patients with lung cancer and 1286 controls from 6 comparative studies were included in this meta-analysis. The results revealed a significant association between the AGT gene T174M polymorphism and MI risk (MM vs TT: OR = 2.87, 95%CI = 1.71-4.83; dominant model: OR = 1.57, 95%CI = 1.10-2.25; recessive model: OR = 0.41, 95%CI = 0.25-0.66). In subgroup analysis by nationality, we observed a significant association between the AGT gene T174M polymorphism and susceptibility to MI in both Caucasian and Asian populations. In conclusion, the T174M polymorphism in the AGT gene may be related to an increased risk of MI. Further larger studies are needed to confirm these conclusions.

Asunto(s)

Angiotensinógeno/genética , Secuencia de Aminoácidos , Estudios de Casos y Controles , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Infarto del Miocardio/genética , Polimorfismo Genético , Riesgo

RESUMEN

AIM: The renal renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. The aim of this study was to investigate sex differences in renal renin-angiotensin system (RAS) and the roles of androgens in diabetes-associated renal injury. METHODS: Renal injury and fibrosis were studied in streptozotocin-induced diabetic rats by albuminuria and by gene expression of collagen I and fibronectin. RAS was investigated by analysing the plasma angiotensinogen (AOGEN) and renin activity (PRA) and their renal gene expression. Also, a group of diabetic rats was treated with the anti-androgen flutamide. RESULTS: Albuminuria was significantly lower in diabetic females than in males (1.2 [0.8-1.5] versus 4.4 [2.2-6.1] mg/24 h, data are median [IQR] values, P < 0.05). Renal AOGEN mRNA levels were increased by diabetes in males (8.1 ± 0.8% in diabetes versus 0.8 ± 0.2% in control, P < 0.001) but not in females (1.0 ± 0.1% in diabetes versus 0.8 ± 0.1% in control, P > 0.05), as were collagen I and fibronectin mRNAs. Furthermore, AOGEN mRNA levels were strongly correlated with albuminuria (Spearman r = 0.64, 95% [CI] 0.36-0.81, P < 0.0001). Diabetes decreased PRA, renal renin mRNA and plasma AOGEN in both females and males. Anti-androgen treatment decreased albuminuria only in diabetic males without affecting the endocrine or renal RAS. CONCLUSIONS: These data indicate that renal but not hepatic AOGEN or renin is positively associated with diabetic albuminuria and contribute to the sex-dependent differences in renal injury. Androgens may contribute to albuminuria in male independently of the RAS.

Asunto(s)

Angiotensinógeno/sangre , Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/etiología , Riñón/metabolismo , Sistema Renina-Angiotensina , Albuminuria/sangre , Albuminuria/etiología , Antagonistas de Andrógenos/farmacología , Angiotensinógeno/genética , Animales , Biomarcadores/sangre , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Diabetes Mellitus Experimental/sangre , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Femenino , Fibronectinas/genética , Fibronectinas/metabolismo , Fibrosis , Flutamida/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Masculino , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Renina/sangre , Renina/genética , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Factores de Riesgo , Factores Sexuales