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1.
Anticancer Res ; 39(10): 5525-5530, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570446

RESUMO

BACKGROUND/AIM: Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes. MATERIALS AND METHODS: DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A. RESULTS: The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls. CONCLUSION: Increased expression of AGT may be associated with BCC.


Assuntos
Carcinoma Basocelular/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinogênio/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(8): 997-1002, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31484268

RESUMO

Objective: To explore the association between preeclampsia/eclampsia and maternal and fetal angiotensinogen SNPs. Methods: From January 2008 to October 2015, a case-parents/mother-control designed study was conducted among 347 preeclampsia/eclampsia cases and 700 controls to collect related information on their demographic characteristics and to detect the related angiotensinogen SNPs' genotypes. Both log-linear and unconditional logistic regression methods were employed to investigate the genetic effects of maternal/fetal angiotensinogen SNPs on preeclampsia/eclampsia. Multivariate binary unconditional logistic regression model and covariance were used to analyze the relationship between BMI before pregnancy, weight gain during pregnancy and overweight and obesity in preschool children. Results: Both fetal angiotensinogen rs3789679 GA and AA genotype were associated with the reduced risks of preeclampsia/eclampsia, with ORs as 0.73 (95%CI: 0.55-0.96) and 0.62 (95%CI: 0.39-0.98), respectively. For fetal angiotensinogen rs2493132, individuals that carrying the TT genotype, presented a positive association with the risk of preeclampsia/eclampsia, with OR as 1.60 (95%CI: 1.08-2.37). However, these associations were not statistically significant after the correction of the false discovery rate. It was observed that fetal rs3789679 could reduce the risk of preeclampsia/eclampsia (OR=0.73, 95%CI: 0.55-0.96) under the dominant model (GA+AA/GG) while fetal rs2493132 increased the risk of preeclampsia/eclampsia (OR=1.66, 95%CI: 1.13-2.44) under the recessive model (TT/CC+CT). Maternal rs5051 presented an association with preeclampsia/eclampsia (OR=1.33, 95%CI: 1.01-1.76) under the dominant model (TC+CC/TT). Conclusions: Results from the dominant model showed that both fetal rs3789679 GA and AA genotype reduced the risk of preeclampsia/eclampsia and maternal rs5051 TC while CC genotype increased the risk of preeclampsia/eclampsia. Fetal rs2493132 TT genotype seemed to be associated with the risk of preeclampsia/eclampsia under the recessive model.


Assuntos
Angiotensinogênio/genética , Eclampsia/genética , Polimorfismo de Nucleotídeo Único/genética , Pré-Eclâmpsia/genética , Angiotensinogênio/sangue , Estudos de Casos e Controles , Eclampsia/sangue , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pré-Eclâmpsia/sangue , Gravidez , Cuidado Pré-Natal
3.
Hypertension ; 74(4): 817-825, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31422694

RESUMO

The BBSome-a complex consisting of 8 Bardet-Biedl syndrome proteins-is involved in the regulation of various cellular processes. Recently, the BBSome complex has emerged as an important regulator of cardiovascular function with implications for disease. In this study, we examined the role of the BBSome in vascular smooth muscle and its effects on the regulation of cardiovascular function. Smooth muscle-specific disruption of the BBSome through tamoxifen-inducible deletion of Bbs1 gene-a critical component of the BBSome complex-reduces relaxation and enhances contractility of vascular rings and increases aortic stiffness independent of changes in arterial blood pressure. Mechanistically, we demonstrate that smooth muscle Bbs1 gene deletion increases vascular angiotensinogen gene expression implicating the renin-angiotensin system in these altered cardiovascular responses. Additionally, we report that smooth muscle-specific Bbs1 knockout mice demonstrate enhanced ET-1 (endothelin-1)-induced contractility of mesenteric arteries-an effect reversed by blockade of the AT1 (angiotensin type 1 receptor) with losartan. These findings highlight the importance of the smooth muscle BBSome in the control of vascular function and arterial stiffness through modulation of renin-angiotensin system signaling.


Assuntos
Pressão Sanguínea/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Rigidez Vascular/fisiologia , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Animais , Aorta/fisiologia , Artérias Mesentéricas/fisiologia , Camundongos , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/genética , Vasodilatação/fisiologia
4.
Arch Endocrinol Metab ; 63(4): 402-410, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365628

RESUMO

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.


Assuntos
Obesidade/genética , Sobrepeso/genética , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Adulto , Distribuição por Idade , Angiotensinogênio/genética , Pressão Sanguínea , Índice de Massa Corporal , Brasil , Estudos Transversais , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Distribuição por Sexo , Circunferência da Cintura
5.
J Strength Cond Res ; 33(9): 2344-2351, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31343553

RESUMO

Pickering, C, Suraci, B, Semenova, EA, Boulygina, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Leonska-Duniec, A, Pajak, B, Chycki, J, Moska, W, Lulinska-Kuklik, E, Dornowski, M, Maszczyk, A, Bradley, B, Kana-ah, A, Cieszczyk, P, Generozov, EV, and Ahmetov, II. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 33(9): 2344-2351, 2019-Sprint speed is an important component of football performance, with teams often placing a high value on sprint and acceleration ability. The aim of this study was to undertake the first genome-wide association study to identify genetic variants associated with sprint test performance in elite youth football players and to further validate the obtained results in additional studies. Using micro-array data (600 K-1.14 M single nucleotide polymorphisms [SNPs]) of 1,206 subjects, we identified 12 SNPs with suggestive significance after passing replication criteria. The polymorphism rs55743914 located in the PTPRK gene was found as the most significant for 5-m sprint test (p = 7.7 × 10). Seven of the discovered SNPs were also associated with sprint test performance in a cohort of 126 Polish women, and 4 were associated with power athlete status in a cohort of 399 elite Russian athletes. Six SNPs were associated with muscle fiber type in a cohort of 96 Russian subjects. We also examined genotype distributions and possible associations for 16 SNPs previously linked with sprint performance. Four SNPs (AGT rs699, HSD17B14 rs7247312, IGF2 rs680, and IL6 rs1800795) were associated with sprint test performance in this cohort. In addition, the G alleles of 2 SNPs in ADRB2 (rs1042713 & rs1042714) were significantly over-represented in these players compared with British and European controls. These results suggest that there is a genetic influence on sprint test performance in footballers, and identifies some of the genetic variants that help explain this influence.


Assuntos
Desempenho Atlético/fisiologia , Grupo com Ancestrais do Continente Europeu/genética , Corrida/fisiologia , Futebol/fisiologia , 17-Hidroxiesteroide Desidrogenases/genética , Aceleração , Adolescente , Alelos , Angiotensinogênio/genética , Criança , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fator de Crescimento Insulin-Like II/genética , Interleucina-6/genética , Masculino , Polônia , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Receptores Adrenérgicos beta 2/genética , Federação Russa , Reino Unido , Adulto Jovem
6.
Bull Exp Biol Med ; 167(1): 74-78, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31177447

RESUMO

The study included pregnant women aged 23-41 years with preeclampsia and gestation-associated arterial hypertension at weeks 27-40 and patients with essential arterial hypertension developing under conditions of the metabolic syndrome and without it. Frequency analysis of polymorphisms of the renin-angiotensin system genes (ACE, AGT, and AGTR1), ITGB3, FTO and their associations confirmed the syndrome nature of hypertensive disorders in pregnancy. The presence allele T of AGT gene and/or allele C of AGTR1 gene in the genotype of patients with preeclampsia was associated with higher BP and pressure load over 24 h. Allele D of ACE gene was also essential for BP parameters (pressure load) in patients with preeclampsia and gestation-associated arterial hypertension. Due to high genetic heterogeneity of the preeclampsia syndrome and genetic differences in the incidence of the studied gene polymorphisms in preeclampsia and gestation-associated arterial hypertension, no direct associations between these gestation disorders and polymorphic markers of the renin-angiotensin system genes can be established. However, polymorphisms of the renin-angiotensin system genes are essential for the 24-h dynamics of BP and pressure load under conditions of hypertensive disorders in pregnancy.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Angiotensinogênio/genética , Hipertensão Induzida pela Gravidez/genética , Integrina beta3/genética , Peptidil Dipeptidase A/genética , Receptor Tipo 1 de Angiotensina/genética , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/fisiologia , Adulto , Feminino , Humanos , Polimorfismo Genético/genética , Gravidez , Estudos Prospectivos
7.
Methods Mol Biol ; 1967: 285-293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069778

RESUMO

Angiotensinogen mediates an important role in the pathophysiology of preeclampsia, a disorder of pregnancy characterized by hypertension and proteinuria usually after 20 weeks of gestation. Angiotensinogen is found in two distinct posttranslational forms in the plasma, an oxidized and a reduced (free thiol) form. Higher levels of the oxidized form are associated with an increased risk of preeclampsia. We have developed novel ELISA assays to quantitate the levels of total and free thiol angiotensinogen allowing for calculation of the amount of oxidized angiotensinogen species. We describe the methodology for performing these assays.


Assuntos
Angiotensinogênio/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/métodos , Pré-Eclâmpsia/genética , Prognóstico , Angiotensinogênio/genética , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/patologia , Oxirredução , Pré-Eclâmpsia/patologia , Gravidez
8.
J Physiol Sci ; 69(4): 581-587, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31028527

RESUMO

Hypertension is one of the most important risk factors and a leading cause of death from cardiovascular and cerebrovascular diseases. Based on numerous previous studies, hypertension is thought to be caused by the complex mutual interactions of genetic factors and environmental factors, such as excessive salt intake and stress. However, its detailed mechanisms are not yet clearly understood. The renin-angiotensin system (RAS) is a key hormonal system in the pathogenesis of hypertension. New knowledge is still accruing on this cascade, even after more than 120 years since the discovery of renin. To clarify the molecular mechanisms of RAS in vivo, we created transgenic mice with chronic hypertension. These mice carry the human genes encoding renin, a hypertensive enzyme, and its substrate angiotensinogen. Hypotensive mice homozygous for a targeted disruption of the angiotensinogen gene were also created. This review presents our 47-year history of RAS research.


Assuntos
Sistema Renina-Angiotensina/fisiologia , Angiotensinogênio/genética , Animais , Humanos , Hipertensão/fisiopatologia , Sistema Renina-Angiotensina/genética
9.
Hypertension ; 73(6): 1249-1257, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31030610

RESUMO

Small interfering RNAs (siRNAs) targeting hepatic angiotensinogen ( Agt) may provide long-lasting antihypertensive effects, but the optimal approach remains unclear. Here, we assessed the efficacy of a novel AGT siRNA in spontaneously hypertensive rats. Rats were treated with vehicle, siRNA (10 mg/kg fortnightly; subcutaneous), valsartan (31 mg/kg per day; oral), captopril (100 mg/kg per day; oral), valsartan+siRNA, or captopril+valsartan for 4 weeks (all groups, n=8). Mean arterial pressure (recorded via radiotelemetry) was lowered the most by valsartan+siRNA (-68±4 mm Hg), followed by captopril+valsartan (-54±4 mm Hg), captopril (-23±2 mm Hg), siRNA (-14±2 mm Hg), and valsartan (-10±2 mm Hg). siRNA and captopril monotherapies improved cardiac hypertrophy equally, but less than the dual therapies, which also lowered NT-proBNP (N-terminal pro-B-type natriuretic peptide). Glomerular filtration rate, urinary NGAL (neutrophil gelatinase-associated lipocalin), and albuminuria were unaffected by treatment. siRNA lowered circulating AGT by 97.9±1.0%, and by 99.8±0.1% in combination with valsartan. Although siRNA greatly reduced renal Ang (angiotensin) I, only valsartan+siRNA suppressed circulating and renal Ang II. This coincided with decreased renal sodium hydrogen exchanger type 3 and phosphorylated sodium chloride cotransporter abundances. Renin and plasma K+ increased with every treatment, but especially during valsartan+siRNA; no effects on aldosterone were observed. Collectively, these data indicate that Ang II elimination requires >99% suppression of circulating AGT. Maximal blockade of the renin-angiotensin system, achieved by valsartan+siRNA, yielded the greatest reduction in blood pressure and cardiac hypertrophy, whereas AGT lowering alone was as effective as conventional renin-angiotensin system inhibitors. Given its stable and sustained efficacy, lasting weeks, RNA interference may offer a unique approach to improving therapy adherence and treating hypertension.


Assuntos
Angiotensinogênio/genética , Pressão Sanguínea/fisiologia , Regulação da Expressão Gênica , Hipertensão/tratamento farmacológico , Fígado/metabolismo , RNA Interferente Pequeno/administração & dosagem , Angiotensinogênio/biossíntese , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão/genética , Hipertensão/metabolismo , Injeções Subcutâneas , Masculino , RNA/genética , RNA Interferente Pequeno/farmacocinética , Ratos , Ratos Endogâmicos SHR
11.
J Clin Lab Anal ; 33(5): e22881, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30912862

RESUMO

OBJECTIVE: To assess the association of gene polymorphisms of angiotensinogen (AGT), the key factor in rennin-angiotensin-aldosterone system (RAAS), with high-sensitivity C-reactive protein (hs-CRP) and coronary artery disease (CAD). METHODS: The current study recruited the patients who were hospitalized and assessed by coronary angiography for suspected CAD. The patients with documented CAD served as CAD group (n = 492) while the patients without documented CAD (n = 87) served as control group. We compared laboratory data and CAD risk factors between the two groups. Furthermore, we analyzed the association of AGT M235T, G217A, G152A, G-6A, A-20C genotypes with coronary artery stenosis and in-stent restenosis. RESULTS: There were significantly differences between two patient groups in sex, smoking history, diabetes mellitus, carotid atherosclerosis, lower limb arteriosclerosis, hs-CRP, blood glucose, and the level of high-density lipoprotein (HDL; P < 0.05). In CAD group, hs-CRP levels increased with increasing number of coronary artery branches (1, 2, or ≥3; P < 0.01), and Gensini integral was positively correlated with hs-CRP levels (r = 0.361, P < 0.01). Frequencies of genotype and allele distribution in individual angiotensinogen loci (M235T, G217A, G152A, G-6A, A-20C) did not differ in two patient groups. Following stratification of patients according to hs-CRP levels (<1 mg/L, 1-3 mg/L, and >3 mg/L), the distribution frequency of allele M235T was statistically different among the groups (P < 0.05). CONCLUSION: In CAD patients, M235T among several AGT gene polymorphisms is associated with elevated hs-CRP levels with AGT C allele as the significant factor for patients with hs-CRP level of more than 1 mg/L.


Assuntos
Angiotensinogênio/genética , Proteína C-Reativa/análise , Doença da Artéria Coronariana/genética , Polimorfismo Genético , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Proteína C-Reativa/genética , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Dis Markers ; 2019: 2849695, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30719178

RESUMO

Background: Kawasaki disease (KD) is an acute vasculitis disease that commonly causes acquired heart disease in children. Coronary artery aneurysm (CAA) is a major complication of KD. However, the pathogenesis of KD remains unclear. The results of a genome-wide association study (GWAS) showed that two functional single-nucleotide polymorphisms (SNPs; rs699A>G and rs5050T>G) in the angiotensinogen (AGT) gene were related to cardiovascular disease susceptibility. The purpose of our study was to estimate the relationship between the two GWAS-identified AGT gene polymorphisms and the risk of CAA in Southern Chinese children with KD. Methods: We genotyped the two AGT gene polymorphisms (rs699A>G and rs5050T>G) in 760 KD cases and 972 healthy controls. We used the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the degree of the associations. Results: These two AGT gene polymorphisms were not associated with a risk of KD relative to the controls, but after adjusting for sex and age, the carriers of the rs5050G allele with TG/GG vs TT had an adjusted OR = 1.56, 95% CI = 1.01-2.41, and P = 0.044 relative to the carriers of the rs5050TT genotype. The susceptibility to CAA was more predominant in KD patients younger than 12 months old. Conclusions: Our results indicate that the AGT gene polymorphism rs5050T>G may increase the risk of CAA in children with KD, especially those who are younger than 12 months. These results need to be verified by a validation study with a larger sample size.


Assuntos
Angiotensinogênio/genética , Aneurisma Coronário/genética , Síndrome de Linfonodos Mucocutâneos/complicações , Polimorfismo de Nucleotídeo Único , Criança , Pré-Escolar , China , Aneurisma Coronário/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
13.
Hereditas ; 156: 6, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30700972

RESUMO

Background: To determine if the rs7079 polymorphism located in the 3' UTR of the angiotensinogen gene (AGT) altered AGT gene expression and the risk of lead poisoning. A case-control study and luciferase reporter gene assay identified a significant association between rs7079 variants and the risk of lead poisoning. Results: Serum AGT levels were significantly higher in individuals carrying the rs7079 CA genotype, as compared to those carrying the rs7079 CC genotype. The binding of the miRNA mimics miR-31-5p and miR-584-5p to the 3' UTR of AGT differed based on which rs7079 variant was present, implying that AGT gene expression depends on the rs7079 variant carried. Conclusions: The rs7079 C to A substitution reduced the binding of miR-31-5p/miR-584-5p to the 3' UTR of AGT, possibly altering the risk of lead poisoning.


Assuntos
Angiotensinogênio/genética , Intoxicação por Chumbo/genética , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Adulto Jovem
14.
Pathol Res Pract ; 215(5): 893-899, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30718100

RESUMO

AIM: The present study aims to identify aberrantly methylated and differentially expressed genes (DEGs) in gastric cancer (GC) and explore their potential role in the carcinogenesis and development of GC. METHODS: The original RNA-Seq, clinical information and Illumina Human Methylation 27 Chip data associated with GC were downloaded from The Cancer Genome Atlas (TCGA) database using the gdc-client tool. The DEGs and aberrantly methylated genes (AMGs) were screened with edgeR and limma package in R, respectively. The cut-off criteria for DEG identification were P < 0.05 and fold change (FC) >2.0, and for AMG identification were P < 0.05 and |t|>2.0. Genes which were both DEGs and AMGs were considered to be regulated by aberrant DNA methylation in GC. The common genes were used for further functional enrichment analysis in the categories of cellular component, molecular function, biological process and biological pathway. RESULTS: In total 465 genes including 336 down-regulated genes with hyper-methylation (DGs-Hyper) and 129 up-regulated genes with hypo-methylation (UGs-Hypo) were identified. Cellular component analysis showed that these genes were mainly expressed in the cytoplasm and plasma membrane. Molecular function and biological process analysis indicated that the genes primarily participate in cell communication, signal transduction, cell growth/maintenance and function as transcription factors, receptor, cell adhesion molecules, and transmembrane receptor protein tyrosine kinases. Biological pathway analysis revealed that the genes are involved in some crucial pathways including epithelial-to-mesenchymal transition, IL3-mediated signaling, mTOR signaling, VEGF/VEGFR and c-Met signaling. KRT15, INHBA, MATN3, and AGT are significantly associated with the prognosis of GC patients. CONCLUSION: Our study identified several DEGs regulated by aberrant DNA methylation in GC. The mechanism of DNA methylation in the carcinogenesis and development of GC could be further explored in these genes, especially KRT15, INHBA, MATN3, and AGT.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Gástricas/genética , Transcriptoma/genética , Adulto , Idoso , Angiotensinogênio/genética , Biologia Computacional , Metilação de DNA , Bases de Dados Genéticas , Feminino , Humanos , Subunidades beta de Inibinas/genética , Queratina-15/genética , Masculino , Proteínas Matrilinas/genética , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
15.
J Renin Angiotensin Aldosterone Syst ; 20(1): 1470320319827205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798697

RESUMO

INTRODUCTION:: This study aimed to investigate whether mononucleotide polymorphisms of the angiotensinogen gene at promoter were associated with the blood-pressure-lowering response to telmisartan treatment. MATERIALS AND METHODS:: After a two-week single-blind placebo run-in period, 148 patients with mild-to-moderate primary hypertension received monotherapy with 80 mg/day of telmisartan and then were followed up for eight weeks. The -6A/G and -20A/C polymorphisms of the angiotensinogen gene at promoter were determined through polymerase chain reaction and restriction fragment length polymorphsim analysis. The relationship between these polymorphisms and changes in blood pressure was observed and evaluated after eight weeks of treatment. RESULTS:: There were no significant differences between -6A/G, -20A/C polymorphisms of the angiotensinogen gene and blood pressure reductions after treatment, p>0.05. CONCLUSION:: It is suggested that angiotensinogen-6 A/G and angiotensinogen-20 A/C polymorphisms were not associated with the antihypertensive response to telmisartan treatment in Chinese patients with hypertension.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Angiotensinogênio/genética , Anti-Hipertensivos/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença , Hipertensão/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/genética , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Telmisartan/farmacologia , Telmisartan/uso terapêutico , Adulto Jovem
16.
J Renin Angiotensin Aldosterone Syst ; 20(1): 1470320318823927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798724

RESUMO

OBJECTIVE:: Although the angiotensinogen ( AGT) gene T174M polymorphism has been implicated in the pathogenesis of diabetic nephropathy (DN), study results have been inconsistent. The present meta-analysis was conducted to determine the correlation of AGT T174M polymorphism with DN. METHODS:: We retrospectively extracted relevant studies from Embase as well as PubMed databases. Additionally, a fixed- or random-effects model was employed for calculation of pooled odds ratio (OR) along with 95% confidence interval (CI). RESULTS:: In total, we identified six studies (1179 cases and 927 controls) regarding the AGT gene T174M polymorphism. The pooled ORs for the association between the AGT T174M polymorphism and DN risk were not statistically significant under all genetic models (M vs T: OR = 1.22, 95% CI = 0.84-1.75; MM vs TT: OR = 1.94, 95% CI = 0.93-4.04; MT vs TT: OR = 1.11, 95% CI = 0.76-1.63; the dominant model: OR =1.19, 95% CI = 0.80-1.77; the recessive model: OR = 1.94, 95% CI = 0.93-4.03). Subgroup analyses based on the type of race showed the M allele of the AGT T174M polymorphism increased DN risk in Asians, but not in Caucasians. CONCLUSIONS:: Our study indicated that the T174M polymorphism in the AGT gene was associated with DN in Asians.


Assuntos
Angiotensinogênio/genética , Nefropatias Diabéticas/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Humanos , Razão de Chances , Viés de Publicação , Fatores de Risco
17.
J Strength Cond Res ; 33(6): 1505-1511, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26840443

RESUMO

Ben-Zaken, S, Eliakim, A, Nemet, D, and Meckel, Y. Genetic variability among power athletes: the stronger vs. the faster. J Strength Cond Res XX(X): 000-000, 2019-Athletic events can be divided into "aerobic-type events" or "anaerobic-type events" based on energy usage. Power, speed, and strength are also used to specify sports subtypes. Weightlifters (WLs), sprinters, and jumpers feature high-intensity efforts lasting a few seconds. However, their performance requires different proportions of power, speed, and strength. The aim of the current study was to examine genetic differences between subtypes of anaerobic athletes in 3 genetic variants: ACTN3 R577X, which is associated with muscle contractions; AGT Met235Thr which is associated with muscle growth; and PPARD T/C, which is associated with aerobic capacity. Seventy-one sprinters and jumpers (S/J), 54 WLs, and 86 controls participated in the study. Genomic DNA was extracted from peripheral blood using a standard protocol. Genotypes were determined using a TaqMan allelic discrimination assay. The ACTN3 RR genotype frequency was significantly higher among S/J (39.4%) compared with WLs (22.2%) and controls (18.6%). The AGT Thr-Thr genotype frequency was significantly higher among WLs (25.9%) compared with S/J (4.2%) and controls (12.8%). PPARD T294C genotype frequencies did not differ between groups. The results suggest that there may be a specific genetic makeup enabling an athlete to excel in speed-oriented events (sprints), rather than in strength-oriented events (weightlifting).


Assuntos
Actinina/genética , Angiotensinogênio/genética , Desempenho Atlético/fisiologia , PPAR delta/genética , Corrida/fisiologia , Levantamento de Peso/fisiologia , Adolescente , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/genética , Força Muscular/genética , Músculo Esquelético/crescimento & desenvolvimento , Consumo de Oxigênio/genética , Polimorfismo Genético , Adulto Jovem
18.
Mol Biol Rep ; 46(1): 443-449, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30478747

RESUMO

Angiotensin II (Ang II: a truncated octapeptide of angiotensinogen, AGT) and 11-ß-hydroxylase influence regulation of blood pressure. Dysregulation of Ang II and 11-ß-hydroxylase can lead to hypertension and elevate aldosterone levels. Polymorphisms in AGT (encodes AGT) and CYP11B1 (encodes 11-ß-hydroxylase) shift the paradigm from physiological to pathological. Currently, various high-throughput techniques are used to genotype these polymorphisms. These techniques require expensive infrastructure and reagents. However, in developing countries, where cost is the main limiting factor, it is not feasible to use expensive techniques. So, the aim of current study was to develop efficient low-cost method for genotyping of cardiovascular disease and hypertension associated polymorphisms of AGT (rs4762, rs5051) and CYP11B1 (rs6410). For this, tetra amplification-refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was developed and optimized for aforementioned AGT and CYP11B1 gene polymorphisms. Efficiency of T-ARMS-PCR was tested by genotyping 776 human samples. These T-ARMS-PCR assays were also validated by Sanger DNA sequencing, where 100% concordance was found, allowing the efficient use of these T-ARMS-PCR assays for polymorphism genotyping in AGT and CYP11B1 in resource limited settings. T-ARMS-PCR is low-cost, efficient and reliable assay for genotyping of AGT and CYP11B1 gene polymorphisms.


Assuntos
Angiotensinogênio/análise , Técnicas de Genotipagem/métodos , Esteroide 11-beta-Hidroxilase/análise , Alelos , Angiotensina II/genética , Angiotensinogênio/genética , Pressão Sanguínea/genética , Doenças Cardiovasculares/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Hipertensão/genética , Masculino , Peptidil Dipeptidase A/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único/genética , Sistema Renina-Angiotensina/genética , Esteroide 11-beta-Hidroxilase/genética
19.
Biosci Rep ; 39(1)2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30530571

RESUMO

Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.


Assuntos
Angiotensinogênio/genética , Anti-Hipertensivos/farmacologia , Terapia Genética/métodos , Hipertensão/terapia , Oligonucleotídeos Antissenso/genética , Sistema Renina-Angiotensina/genética , Angiotensinogênio/antagonistas & inibidores , Angiotensinogênio/metabolismo , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Rim/metabolismo , Fígado/metabolismo , Terapia de Alvo Molecular , Oligonucleotídeos Antissenso/síntese química , Oligonucleotídeos Antissenso/metabolismo , Ratos Endogâmicos SHR
20.
J Stroke Cerebrovasc Dis ; 28(2): 441-449, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30409744

RESUMO

BACKGROUND: Cerebrovascular stroke is a common critical complication of sickle cell disease (SCD). Angiotensinogen (AGT) M235T gene polymorphism is associated with risk of ischemic stroke and cardiovascular disease. AIM: We investigated the potential association between angiotensinogen M235T gene polymorphism and susceptibility to cerebrovascular and cardiopulmonary complications in adolescents with SCD. METHODS: Forty-six patients with SCD in steady state were studied stressing on history of stroke, hydroxyurea/chelation therapy, hematological profile, and echocardiographic findings. Polymerase chain reaction-based restriction fragment length polymorphism analysis was used to detect AGT M235T gene polymorphism. Fifty sex- and age-matched healthy controls were enrolled for assessment of M235T gene polymorphism pattern. RESULTS: The distribution of AGT M235T gene polymorphism was similar between SCD patients and healthy controls. The frequency of T allele of AGT M235T gene polymorphism (TT and MT genotypes) was significantly higher among patients with history of manifest stroke (P < .001). Patients with TT and MT genotypes had higher incidence of cardiopulmonary complications (P = .041) as well as higher percentage of HbS (P < .001) and lower hemoglobin level (P = .008) compared with those with MM genotype. Serum ferritin, liver iron concentration, and cardiac T2* were not related to T alleles or genotypes. Logistic regression analysis revealed that M235T genotype was a significant independent factor related to the occurrence of stroke among patients with SCD (Odds Ratio 14.05, 95% confidence interval 3.82-28.91; P = .001). CONCLUSION: AGT M235T gene polymorphism may represent a genetic modifier to vascular morbidities in Egyptian patients with SCD.


Assuntos
Anemia Falciforme/genética , Angiotensinogênio/genética , Transtornos Cerebrovasculares/genética , Genes Modificadores , Cardiopatias/genética , Pneumopatias/genética , Polimorfismo Genético , Adolescente , Fatores Etários , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Estudos de Casos e Controles , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/epidemiologia , Egito/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Humanos , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Masculino , Fenótipo , Fatores de Risco , Adulto Jovem
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