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1.
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
2.
Pan Afr Med J ; 32: 197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312309

RESUMO

Introduction: Just recently, it has been established that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is linked to the pathogenesis and to the evolution of human cancers. Therefore, the present study was concerned with the investigation of an eventual association between glioma and I/D polymorphism of the ACE gene. Methods: The expression of ACE gene was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis in 36 Algerian patients with glioma and 195 healthy controls. Results: In glioma cases, allelic frequencies and genotypes distribution of the ACE I/D polymorphism were different from controls cases. ACE DD genotype were highly presented in glioma cases (63.9%) than controls (33.8%) and conferred 3.64-fold risk for predisposition in glioma cases (vs ID genotype, p<0.001). Recessive model (ACE II + ID genotypes vs DD) was associated with a 72% reduced risk of glioma (OR = 0.28, 95% CI: 0.13-0.60, p <0.001). Per copy D allele frequency was found higher in glioma cases (79.2%) than in controls (63.3 %), OR = 2.20, 95% CI: 1.20 - 4.03, p = 0.009. Conclusion: The obtained data showed that the presence of the D allele might be a risk factor for the development of glioma. Further studies considering different ethnic groups with large samples are required to confirm this finding.


Assuntos
Neoplasias Encefálicas/genética , Predisposição Genética para Doença , Glioma/genética , Peptidil Dipeptidase A/genética , Adulto , Argélia , Estudos de Casos e Controles , Feminino , Deleção de Genes , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Fatores de Risco
3.
Medicine (Baltimore) ; 98(29): e16476, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335708

RESUMO

The insertion (I) or deletion (D) polymorphism in the angiotension I converting enzyme gene, (ACE I/D, rs1799752) is associated with human exercise endurance and performance. However, most of the aforementioned studies focus on marathons, swimming, and triathlons, while the ACE polymorphism in ultra-marathoners has not yet been reported. We studied the impact of ACE I/D polymorphism in ultra-marathoners and investigated its relationship with lipid profiles, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) levels in runners before and after ultra-marathon racing.This observational study used data from a 100-km ultra-marathon in Taipei, Taiwan. Twenty-four male participants were analyzed for their ACE insertion/deletion polymorphism, lipid profiles, hs-CRP, IL-6 in serum immediately before and after ultra-marathon running.In our 24 subjects analyzed, 7, 14, and 3 subjects were of I/I, I/D, and D/D genotypes, respectively. Runners with the D polymorphism (I/D and D/D) showed a trend of better performance in the 100-km ultra-marathon (measured by completion time in minutes, P = .036). In this group, the previous best marathon performance was also significantly better than the I/I group (P = .047). After adjusting for body mass index (BMI), the difference in performance was not significant. Ketone levels, IL-6, and hs-CRP levels were highly increased at immediately and 24-hour post-race. No correlation was found between different ACE polymorphisms and common biochemical parameters examined.We report the first study in the impact of the ACE I/D (rs1799752) on ultra-marathoners. Presence of the D polymorphism in ACE gene is associated with better performance, although the BMI of the runners contribute as a major factor. There was no difference in the biochemical or lipid parameters measured among different ACE polymorphisms.


Assuntos
Proteína C-Reativa/metabolismo , Interleucina-6/sangue , Lipídeos/sangue , Peptidil Dipeptidase A/genética , Resistência Física/fisiologia , Polimorfismo Genético , Corrida/fisiologia , Adulto , Alelos , Índice de Massa Corporal , Genótipo , Humanos , Cetonas/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Rev Assoc Med Bras (1992) ; 65(6): 923-929, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340327

RESUMO

OBJECTIVE: To investigate the association between genotype insertion or deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and susceptibility to coronary artery disease (CAD) in Chinese Han population. METHODS: We conducted a comprehensive search for the OR value of contrast between the group of genotype insertion or deletion polymorphism of the ACE and the group of CAD as an effective index. A meta-analysis (Stata 12.0) was used to test the heterogeneity of the results, combine the values for effect, conduct sensitivity analysis, and basic evaluation. RESULTS: A total of 638 studies were found on the association between polymorphisms of the angiotensin-converting enzyme gene and CAD, of which 44 studies met the inclusion criteria. In total, our study included 5619 cases and 4865 controls. The heterogeneity test of each study (P < 0.001) was carried out using a random effect model. The OR value of DD/ID+II was 1.95, 95% confidence interval (95%CI) (1.66-2.29). The OR value of II/DI+DD was 0.63, 95%CI (0.55-0.72). The funnel figure is basically symmetrical and the results of the sensitivity analysis were stable. CONCLUSION: The DD genotype of the angiotensin converting enzyme gene may be a weaker risk factor for CAD in the Chinese Han population.


Assuntos
Doença da Artéria Coronariana/genética , Estudos de Associação Genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , China/etnologia , Doença da Artéria Coronariana/etnologia , Humanos , Fatores de Risco
5.
Virology ; 533: 137-144, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31247402

RESUMO

Angiotensin-converting enzyme (ACE) plays diverse roles in the animal kingdom. However, whether ACE plays an immune function against viral infection in vector insects is unclear. In this study, an ACE gene (LsACE) from the small brown planthopper was found to respond to Rice stripe virus (RSV) infection. The enzymatic activities of LsACE were characterized at different pH and temperature. Twenty planthopper proteins were found to interact with LsACE. RSV infection significantly upregulated LsACE expression in the testicle and fat body. When the expression of LsACE in viruliferous planthoppers was inhibited, the RNA level of the RSV SP gene was upregulated 2-fold in planthoppers, and all RSV genes showed higher RNA levels in the rice plants consumed by these planthoppers, leading to a higher viral infection rate and disease rating index. These results indicate that LsACE plays a role in the immune response against RSV transmission by planthoppers.


Assuntos
Hemípteros/imunologia , Hemípteros/virologia , Proteínas de Insetos/imunologia , Insetos Vetores/imunologia , Insetos Vetores/virologia , Peptidil Dipeptidase A/imunologia , Tenuivirus/fisiologia , Sequência de Aminoácidos , Animais , Hemípteros/genética , Hemípteros/fisiologia , Proteínas de Insetos/genética , Insetos Vetores/genética , Insetos Vetores/fisiologia , Oryza/virologia , Peptidil Dipeptidase A/genética , Filogenia , Doenças das Plantas/virologia , Tenuivirus/classificação , Tenuivirus/genética , Tenuivirus/isolamento & purificação
6.
Med Sci Monit ; 25: 3390-3396, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064975

RESUMO

BACKGROUND This study aimed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion polymorphisms with left ventricular hypertrophy (LVH) in Han and Uighur hypertension-OSAHS (obstructive sleep apnea hypopnea syndrome) patients in China. MATERIAL AND METHODS A total of 162 Han and 72 Uygur patients with hypertension-OSAHS were independently subdivided into an LVH group and a non-LVH (NLVH) group based on the left ventricular mass index. The insertion/deletion polymorphisms of ACE gene were determined by polymerase chain reaction. The association of ACE gene insertion/deletion polymorphisms with LVH was assessed by chi-squared test. Logistic regression analysis was performed to obtain the odds ratios and 95% confidence intervals for the risk of LVH after adjusting for confounding factors. RESULTS In Uighur patients, the distributions of D allele and DD genotype showed significant differences between the LVH group and the NLVH group. The difference of DD genotype remained significant after multivariate adjustment. In contrast, no significant differences were observed in the distributions of D allele and DD genotype between the LVH group and the NLVH group in Han patients. Moreover, moderate-severe OSAHS was an independent risk factor for LVH. CONCLUSIONS D allele and DD genotype of ACE gene are possible genetic markers for the risk of LVH in Uighur but not Han hypertension-OSAHS patients.


Assuntos
Hipertrofia Ventricular Esquerda/genética , Peptidil Dipeptidase A/genética , Apneia Obstrutiva do Sono/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , China , Grupos Étnicos/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Hipertensão/complicações , Hipertensão/genética , Hipertrofia Ventricular Esquerda/fisiopatologia , Mutação INDEL/genética , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/fisiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Fatores de Risco , Apneia Obstrutiva do Sono/complicações
7.
Ter Arkh ; 91(1): 71-77, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090375

RESUMO

AIM: To evaluate the association of a complex of cardiovascular risk factors and genetic markers with the development of high albuminuria among patients with arterial hypertension in the population of Mountain Shoriya, taking into account ethnicity. MATERIALS AND METHODS: A clinical epidemiological study of a compactly residing population in remote areas of Mountain Shoria was carried out. 1409 people were examined [901 people - representatives of the indigenous nationality (Shorians), 508 people - representatives of non-indigenous nationality (90% of them are Caucasians)]. Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and instrumental investigation. To study the state of the kidneys, the concentration (the presence of elevated levels) of albumin (albuminuria) in the morning portion of urine by an immunoturbidimetric method was analyzed. Polymorphisms of genes ACE (I/D, rs4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs28365031), MTHFR (c.677С>Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using PCR. RESULTS: In the group of shors with arterial hypertension, high albuminuria was associated with polymorphisms of the ACE genes (OR=2.05), ADRA2B (OR=6.00), elevated triglyceride level (OR=2.86), decreased index of cholesterol of high density lipoproteins (OR=5.57) and increased index of low density lipoproteins (OR=2.49); in the new population - with polymorphisms of the AGTR1 genes (OR=8.66), ADRA2B (OR=6.53), MTHFR (OR=7.16), obesity (OR=2.72), and abdominal obesity (OR=3.14). CONCLUSION: The primary predictors determining the development of high albuminuria among patients with arterial hypertension in both ethnic groups were genetic ones. In addition to them, non-genetic risk factors also contributed to the development of this organ damage to the kidneys: age and lipid metabolism disorders in representatives of indigenous nationality; age and abdominal obesity in the examined patients non-indigenous nationality.


Assuntos
Albuminas/metabolismo , Albuminúria/etnologia , Doenças Cardiovasculares/genética , Grupos Étnicos/genética , Hipertensão/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Peptidil Dipeptidase A/genética , Receptor Tipo 1 de Angiotensina/genética , Receptores Adrenérgicos alfa 2/genética , Albuminúria/genética , Doenças Cardiovasculares/etnologia , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Hipertensão/etnologia , Lipoproteínas HDL/metabolismo , Obesidade Abdominal/etnologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Fatores de Risco , Federação Russa/epidemiologia , Triglicerídeos/metabolismo
8.
J Genet ; 982019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945668

RESUMO

The aim of this study was to determine whether the polymorphism of aldosterone synthase (CYP11B2) -344C/T and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) were associated with the response of blood pressure (BP) to telmisartan treatment. After a two-week single-blind placebo run-in period, 148 patients with mild-to-moderate primary hypertension received monotherapy of telmisartan with 80 mg/day and then were followed up for eight weeks. Polymorphisms of CYP11B2 -344C/T and ACE I/D gene were determined through polymerase chain reaction-restriction fragment polymorphism analysis. The relationship between these polymorphisms and changes in BP was monitored and evaluated after eight weeks of treatment. With respect tothe polymorphism of CYP11B2 -344C/T, the reduction in diastolic BP was significantly greater in patients carrying the C allele (CC+CT) compared with those carrying the TT genotype. There was no significant differences between ACE I/D polymorphism and BP reduction after treatment. We concluded that the aldosterone synthase -344C/T polymorphism was related to the antihypertensive treatment with telmisartan in hypertensive patients.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Pressão Sanguínea , Citocromo P-450 CYP11B2/genética , Hipertensão/genética , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único , Telmisartan/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Seguimentos , Genótipo , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Método Simples-Cego , Adulto Jovem
9.
J Exp Clin Cancer Res ; 38(1): 173, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023337

RESUMO

BACKGROUND: Breast cancer angiogenesis is key for metastasis and predicts a poor prognosis. Angiotensin-converting enzyme 2 (ACE2), as a member of the renin-angiotensin system (RAS), was reported to restrain the progression of hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) through inhibiting angiogenesis. However, the relationship between ACE2 and breast cancer angiogenesis remains unclear. METHODS: The prognosis and relative gene selection were analysed using the GEPIA, GEO, TCGA and STRING databases. ACE2 expression in breast cancer tissue was estimated by reverse transcription-quantitative polymerase chain reaction (qPCR). Breast cancer cell migration, proliferation and angiogenesis were assessed by Transwell migration, proliferation, tube formation, and wound healing assays. The expression of vascular endothelial growth factor A (VEGFa) was detected by qPCR and Western blotting. The phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated protein kinase 1/2 (ERK1/2) was examined by Western blotting. Breast cancer metastasis and angiogenesis in vivo were measured using a zebrafish model. RESULTS: ACE2 was downregulated in breast cancer patients. Patients with higher ACE2 expression had longer relapse-free survival (RFS). In vitro, ACE2 inhibited breast cancer migration. Meanwhile, ACE2 in breast cancer cells inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, tube formation and migration. In the zebrafish model, ACE2 inhibited breast cancer cell metastasis, as demonstrated by analyses of the number of disseminated foci and the metastatic distance. Neo-angiogenesis was also decreased by ACE2. ACE2 downregulated the expression of VEGFa in breast cancer cells. Furthermore, ACE2 in breast cancer cells inactivated the phosphorylation of VEGFR2, MEK1/2, and ERK1/2 in HUVECs. CONCLUSIONS: Our findings suggest that ACE2, as a potential resister to breast cancer, might inhibit breast cancer angiogenesis through the VEGFa/VEGFR2/ERK pathway. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Neoplasias da Mama/genética , Neovascularização Patológica/genética , Peptidil Dipeptidase A/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Animais , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Sistema de Sinalização das MAP Quinases/genética , Células MCF-7 , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Fosforilação , Peixe-Zebra
10.
Genet Test Mol Biomarkers ; 23(5): 316-324, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942616

RESUMO

Objective: Perindopril is an angiotensin-converting enzyme (ACE) inhibitor that is commonly used in the treatment of Chinese Han patients with acute myocardial infarction (AMI). However, there have been few studies on whether polymorphisms of the ACE gene affect the efficacy of perindopril or the prognosis of AMI patients. The purpose of this study was to analyze the relationship among the ACE rs121912703 (C>T), rs767880620 (C>A), and rs397514689 (C>T) gene polymorphisms and the prognosis of AMI patients and the clinical efficacy of perindopril in the treatment of AMI. Methods: The ACE genotypes at the rs121912703, rs767880620, and rs397514689 loci in 225 AMI patients treated with perindopril were determined by polymerase chain reaction/Sanger sequencing. Differences in cardiac structure, functional indicators, hemodynamic parameters, and related laboratory indicators were detected before and after treatment. Results: After administration of perindopril, improved ventricular remodeling in AMI patients with wild-type ACE was better than in patients with the ACE rs121912703, rs767880620, and rs397514689 minor variant alleles. The patients harboring wild-type ACE had lower systolic blood pressure and diastolic blood pressure than the patients harboring the minor variant alleles (p < 0.01). The contents of serum ACE and Ang II (angiotensin II) in AMI patients carrying the wild-type ACE alleles were lower than those of patients harboring any of the minor variant alleles (p < 0.01). The 3-year survival time of AMI patients carrying the wild-type ACE alleles was markedly greater compared with AMI patients carrying the mutant genes (p < 0.01). Conclusion: Mutations at the ACE rs121912703, rs767880620, and rs397514689 loci affect the efficacy of perindopril on ventricular remodeling and hemodynamics in Chinese Han AMI patients. The 3-year survival of AMI patients harboring the variant alleles is less than that of the patients harboring the wild-type gene.


Assuntos
Infarto do Miocárdio/genética , Peptidil Dipeptidase A/genética , Perindopril/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Farmacológicos/sangue , China , Grupos Étnicos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Perindopril/metabolismo , Polimorfismo Genético/genética , Resultado do Tratamento
11.
J Renin Angiotensin Aldosterone Syst ; 20(1): 1470320319836302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854921

RESUMO

OBJECTIVE:: Meta-analysis was performed in the current study to evaluate the relationship of the angiotensin-converting enzyme insertion/deletion polymorphism with the risk of the incidence of Henoch-Schönlein purpura. METHODS:: The electronic databases, including Embase, PubMed and Google scholar, were systemically retrieved to search for related articles. Meanwhile, statistical analysis was performed using the odds ratio and the corresponding 95% confidence interval. RESULTS:: A total of six articles enrolling 504 patients and 706 healthy controls was enrolled into the current meta-analysis. Results of the meta-analysis suggested that the angiotensin-converting enzyme D allele was markedly correlated with the risk of the incidence of Henoch-Schönlein purpura among the general population (deletion (D) vs. insertion (I): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.05-1.93; DD vs. II: OR 2.23, 95% CI 1.06-4.70; DI vs. II: OR 1.36, 95% CI 1.00-1.85; dominant model: OR 1.56, 95% CI 1.00-2.42; recessive model: OR 1.83, 95% CI 1.06-3.16). Moreover, such a polymorphism was found to correlate with the susceptibility to Henoch-Schönlein purpura when studies were stratified according to the sample size of over 200. In addition, such a polymorphism was recognised to be remarkably associated with the susceptibility to Henoch-Schönlein purpura in the Caucasian population, which was not found in the Asian population. CONCLUSIONS:: The results of the current meta-analysis indicate that the angiotensin-converting enzyme D allele might be a risk factor against the risk of Henoch-Schönlein purpura, especially in Caucasians.


Assuntos
Predisposição Genética para Doença , Mutação INDEL/genética , Peptidil Dipeptidase A/genética , Púrpura de Schoenlein-Henoch/genética , Grupo com Ancestrais do Continente Europeu/genética , Humanos , Interleucina-18/genética , Viés de Publicação
12.
J Strength Cond Res ; 33(4): 1119-1129, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30908459

RESUMO

Montrezol, FT, Marinho, R, Mota, GdFAd, D'almeida, V, de Oliveira, EM, Gomes, RJ, and Medeiros, A. ACE gene plays a key role in reducing blood pressure in the hyperintensive elderly after resistance training. J Strength Cond Res 33(4): 1119-1129, 2019-Hypertension is a difficult disease to control and exercise training plays a key role in hypertension control. Some individuals are not responsive to exercise training; so, we highlight the polymorphism of I allele of angiotensin-converting enzyme (ACE) as a factor responsible for this lack of responsiveness. The aim of this study was to evaluate the influence of ACE insertion/deletion genotypes on effects of resistance training on blood pressure (BP) and chronic inflammation. Eighty-six hypertensive volunteers, aged between 60 and 80, were evaluated. They performed 16 weeks of resistance training at 50% of 1 maximal repetition. The greatest benefits were seen on homozygous of the Insertion allele, whom presented reduction of systolic blood pressure (SBP: 129.31 ± 13.34 vs. 122.56 ± 9.68 mm Hg, p < 0.001) and diastolic blood pressure (DBP: 79.18 ± 8.05 vs. 70.12 ± 7.71 mm Hg, p < 0.01) during daytime period, and in 24-hour period (SBP: 127.12 ± 13.65 vs. 121.06± 9.68 mm Hg, p < 0.001 and DBP: 71.87 ± 8.39 vs. 68.75 ± 8.72 mm Hg, p < 0.05) and also increased circulating adiponectin levels (4.04 ± 1.79 vs. 6.00 ± 2.81 ng·ml, p < 0.01). Other genotypes showed no changes in BP and biochemical parameters. Our results suggest a cardio protective factor of I allele because only those homozygous showed reductions in BP and increases in adiponectin.


Assuntos
Pressão Sanguínea/genética , Hipertensão/genética , Hipertensão/fisiopatologia , Peptidil Dipeptidase A/genética , Treinamento de Resistência , Adiponectina/sangue , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença Crônica , Exercício/fisiologia , Feminino , Homozigoto , Humanos , Hipertensão/sangue , Mutação INDEL , Inflamação/sangue , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético
13.
J Stroke Cerebrovasc Dis ; 28(6): 1732-1743, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878369

RESUMO

AIMS: The objective of this study was to perform a meta-analysis to evaluate the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and susceptibility to atherosclerosis (AS). METHODS: MEDLINE, EMBASE, and the ISI Web of Science were searched for all eligible published studies concerning the relationship of ACE gene polymorphism with AS without language restrictions. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate this relationship under different genetic models using meta-analytic methods. RESULTS: A total of 15 articles (16 studies) were involved in this meta-analysis. The D allele of the ACE gene had a nonsignificant increase in the risk of AS (D versus I: OR = 1.23, 95% CI, .98-1.53, P = .07; I2 = 87.2%, Pheterogeneity < .01). Compared with the II genotype, the DI (relative risk [RR]: 1.35, 95% CI: 1.09, 1.67, P < .01; I2 = 47.8%, Pheterogeneity = .017) and (DD + DI) (RR = 1.38, 95% CI: 1.04, 1.82, P = .02; I2 = 73.3%, Pheterogeneity < .01) genotype of ACE was associated with higher risk of AS, respectively. Subjects with the DD genotype showed a statistically nonsignificant trend toward greater risk of AS (RR = 1.53, 95% CI: .97, 2.43, P = .07; I2 = 88.6%, Pheterogeneity < .01). Further subgroup analyses showed that significant relationships were only found in Europeans under different gene polymorphism or different genotype models rather than Asians. CONCLUSIONS: The present meta-analysis indicated that the D allele in the ACE gene was associated with the risk of AS, especially in Europeans. Furthermore, increased copy number of D allele was significantly associated with increased AS risk in a dose-dependent manner.


Assuntos
Aterosclerose/genética , Mutação INDEL , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Idoso , Aterosclerose/diagnóstico , Aterosclerose/enzimologia , Aterosclerose/etnologia , Variações do Número de Cópias de DNA , Feminino , Dosagem de Genes , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco
14.
Parasitol Res ; 118(5): 1385-1391, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30919062

RESUMO

Subterranean cavities serve as resting places and hibernation shelters for mosquitoes. In Europe, members of the genus Culex are often the most abundant insects on cave walls. Culex pipiens L., the common house mosquito, exists in two physically very similar, yet genetically and ecologically distinct biotypes (or forms, 'f.'), namely Cx. pipiens f. pipiens and Cx. pipiens f. molestus. Autogeny and stenogamy of the latter form have been interpreted as adaptations to underground habitats. The epigean occurrence of the two biotypes and their hybrids was recently examined in Eastern Austria, but the hypogean distribution of the Cx. pipiens complex and morphologically similar non-members such as Cx. torrentium is unknown. Considering the key role of Culex mosquitoes in the epidemiology of certain zoonotic pathogens, the general paucity of data on species composition and relative abundance in subterranean shelters appears unfortunate.For a first pertinent investigation in Austria, we collected mosquitoes in four eastern federal states. Based on analyses of the ACE2 gene and the CQ11 microsatellite locus, 150 female and three male mosquitoes of the genus Culex, two females of the genus Culiseta and a single female of the genus Anopheles were determined to species level or below. In our catches, Cx. pipiens f. pipiens exceeded the apparent abundance of the purportedly cave-adapted Cx. pipiens f. molestus many times over. Records of Cx. hortensis and Cx. territans, two species rarely collected in Austria, lead us to infer that underground habitats host a higher diversity of culicine mosquitoes than previously thought.


Assuntos
Adaptação Fisiológica/fisiologia , Anopheles/classificação , Cavernas , Culex/classificação , DNA/genética , Ecossistema , Animais , Anopheles/genética , Áustria , Culex/genética , Europa (Continente) , Feminino , Masculino , Repetições de Microssatélites/genética , Peptidil Dipeptidase A/genética
15.
Life Sci ; 225: 39-45, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30917908

RESUMO

AIMS: Renin-angiotensin system modulates cardiac structure independent of blood pressure. The present study aimed at investigating whether single nucleotide polymorphism (SNP) and haplotype of angiotensin converting enzyme 2 (ACE2) could influence blood pressure and the susceptibility to hypertensive left ventricular hypertrophy (LVH). SUBJECTS AND METHODS: A total of 647 patients (347 females and 300 males) with newly diagnosed mild to moderate essential hypertension were enrolled in a blood pressure matched, case-control study. Four ACE2 tagSNPs (rs2074192, rs4646176, rs4646155 and rs2106809) were genotyped and major haplotypes consisting of these four SNPs were reconstructed for all subjects. KEY FINDINGS: In females, minor alleles of ACE2 rs2074192 and rs2106809 respectively conferred a 2.1 and 2.0 fold risk for LVH. ACE2 haplotype TCGT increased the risk for LVH while another haplotype CCGC decreased the risk in females. The covariates-adjusted mean left ventricular mass index was 11% greater in TCGT haplotype carriers than in noncarriers in women. In females, the covariates-adjusted mean systolic blood pressure was 3.4 mm Hg lower in CCGC haplotype carriers than in noncarriers. In males, the covariates-adjusted mean systolic blood pressure was 2.4 mm Hg lower in CCGC haplotype carriers than in noncarriers. SIGNIFICANCE: ACE2 tagSNPs rs2074192 and rs2106809 as well as major haplotypes CCGC and TCGT may serve as novel risk markers for LVH in hypertensive patients.


Assuntos
Marcadores Genéticos , Hipertensão/genética , Hipertrofia Ventricular Esquerda/genética , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Mol Biol Rep ; 46(2): 1835-1843, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30710235

RESUMO

We studied to ascertain whether the ACE and/or CKMM genotypes independently influence the baseline level of some sport performances in 613 inactive male adolescents (mean ± SD age: 13.24 ± 0.28 years). All DNA samples were extracted and genotyped for ACE I/D and CKMM A/G polymorphisms using a PCR based procedure. One-way analysis of covariance was used to examine the discrepancies in the research phenotypes among various ACE and CKMM polymorphisms. The comparisons of genotype and allele frequencies between adolescents with the best and the worst performances were calculated and analyzed by the Chi square test. All procedures were approved by Medical University Ethics Committee. Written informed consent signed and approved by all subject`s parents were obtained. We observed the effect of the ACE and CKMM polymorphisms on VO2max (P = 0.001 & P = 0.001 respectively). ACE and CKMM genotypes differed between groups (< 90th vs. ≥ 90) in the multi-stage 20 m shuttle run (P = 0.001 and 0.001). ACE allele frequencies differed between groups (< 90th vs. ≥ 90) in the multi-stage 20-m shuttle run (P = 0.001). This study suggests that the ACE and CKMM polymorphisms influence the endurance performance phenotype in non-trained adolescent males.


Assuntos
Creatina Quinase Mitocondrial/fisiologia , Peptidil Dipeptidase A/fisiologia , Resistência Física/genética , Adolescente , Desempenho Atlético/fisiologia , Criança , Creatina Quinase Mitocondrial/genética , Exercício/fisiologia , Frequência do Gene , Variação Genética , Genótipo , Humanos , Masculino , Oxigênio/metabolismo , Peptidil Dipeptidase A/genética , Fenótipo , Desempenho Físico Funcional , Polimorfismo Genético
17.
PLoS One ; 14(2): e0211054, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30763326

RESUMO

BACKGROUND: Hypertension is dramatically increasing in Africa with evidence of increased severity and resistance to treatment. Although angiotensin converting enzyme gene polymorphism is associated with higher prevalence of hypertension, the evidence is inconclusive on its influence on the emerging pattern in Africa. This meta-analysis is conducted to pool the available evidence to inform future research and interventions. METHODS: Articles published through May 2018 were systematically searched in PubMed, Scopus and EMBASE databases. Studies were assessed for inclusion by two independent researchers. Six models were used to assess the effect of angiotensin converting enzyme deletion-insertion gene polymorphism. Heterogeneity and publication bias were tested and sensitivity analysis was carried out. Odds ratio and 95% confidence intervals were measured for pooled effect. Both random effect and fixed effect models were used, whilst the frequency of DD, II and DI genotypes were computed and compared. RESULT: Patients with D allele were 1.49 times more likely to develop essential hypertension compared with patients who carry the I allele (OR:1.49; CI:1.07, 2.07). Similarly, patients who had homozygous co-dominance genotype DD (i.e., DD vs II) were at a 2.17 times higher risk of essential hypertension compared to the co-dominant genotype II (OR:2.17, CI:1.79, 3.18), dominant model (I.e., DD+ID vs II) (OR:1.48; CI:1.03, 2.12), and recessive model (OR:1.64; CI:1.03, 2.61). On subgroup analysis, participants from Sub-Saharan Africa were more genetically susceptible to hypertension compared to their North Africa counterparts. There was no publication bias found, but there was high to moderate heterogeneity. CONCLUSION: ACE I/D polymorphism is associated with essential hypertension in Africa in the allele contrast model, as well as the dominant, recessive and homozygous codominance model. On subgroup analysis, ACE I/D was associated with essential hypertension in patients from Sub-Saharan Africa but not in North Africa. A future large scale study, which includes different ethnic groups, is recommended.


Assuntos
Hipertensão/genética , Modelos Genéticos , Peptidil Dipeptidase A/genética , Polimorfismo Genético , África ao Sul do Saara/epidemiologia , África do Norte/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino
18.
In Vivo ; 33(2): 559-562, 2019 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30804141

RESUMO

The association of the high blood pressure D variant of the angiotensin-converting enzyme (ACE) gene with medication-related jaw osteonecrosis (MRONJ) is described in two Greek patients. The first patient, a 73-year-old man, took zolendronate, 4 mg/100 ml IV once per month for two years for prostate cancer and bone metastases. Three months after drug discontinuation, extraction of the first premolar was performed. After the intervention, he suffered from osteonecrosis of the mandible. He presented with hypertension and genetic testing revealed that he was homozygous for the high blood pressure D variant of the ACE gene. The second patient, a 65 years old woman, took denosumab, 120 mg subcutaneously once per month for 6 months for possible bone metastases from breast cancer. Three months after extraction of the first molar, she suffered from MRONJ. He also presented with hypertension and genetic testing revealed that she had the high blood pressure D variant of the ACE gene in a heterozygous state, which moderately predisposes to hypertension. To our knowledge, this is the first report indicating that genetic predisposition to hypertension may increase risk for MRONJ.


Assuntos
Hipertensão/genética , Doenças Maxilomandibulares/genética , Osteonecrose/genética , Peptidil Dipeptidase A/genética , Idoso , Denosumab/efeitos adversos , Testes Genéticos , Heterozigoto , Humanos , Hipertensão/etiologia , Hipertensão/patologia , Doenças Maxilomandibulares/induzido quimicamente , Doenças Maxilomandibulares/complicações , Doenças Maxilomandibulares/patologia , Masculino , Metástase Neoplásica , Osteonecrose/induzido quimicamente , Osteonecrose/complicações , Osteonecrose/patologia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Ácido Zoledrônico/efeitos adversos
19.
Biochem Mol Biol Educ ; 47(2): 168-174, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30694603

RESUMO

For medical students, we combine the laboratory practice with clinical applications by developing biochemical and molecular biology experiments. In this experiment, students first collect their own buccal epithelial cells by a noninvasive mouthwash method. Then, they extract genomic DNA and perform polymerase chain reaction (PCR) to amplify angiotensin-converting enzyme (ACE) gene using genomic DNA as a template. Finally, the polymorphism of ACE gene is observed by electrophoresis. Students not only learn the techniques but also acquire knowledge of the ACE gene polymorphism. By establishing the relationship among ACE polymorphism and high blood pressure and myocardial hypertrophy, students should be able to understand the gene polymorphism and its association with susceptibility to disease. This laboratory practice teaching can also stimulate desire to do scientific research. Experimental results from many individuals can help us determine and analyze the fractions of ACE gene types in Chinese cohorts. Such an experiment strongly activates students and provides a solid foundation for the medical students' future research and clinical application. © 2019 International Union of Biochemistry and Molecular Biology, 47(2): 168-174, 2019.


Assuntos
Células Epiteliais/metabolismo , Laboratórios , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Estudantes de Medicina , Humanos , Peptidil Dipeptidase A/metabolismo
20.
Ecotoxicol Environ Saf ; 170: 188-194, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30529618

RESUMO

Acute and chronic exposure to particulate matter (PM) 2.5 is associated with adverse health effect upon the cardiovascular (CV) system. However, the molecular mechanism by which PM2.5 evokes CV injuries has not been fully clarified. In our recent report, we demonstrate that exposure to PM2.5 leads to elevation of circulating angiotensin II (ANGII) levels and local expressions of angiotensinogen (AGT, the precursor of ANGII), angiotensin-converting enzyme (ACE) and ANGII type 1 receptor (AT1R) in the vascular endothelial cells, which subsequently instigates the oxidative stress and proinflammatory response in the vascular endothelium. In the present study, we disclosed that PM2.5 exposure induced the activation of the transcriptional factor AP-1 and its components, c-Jun and ATF2, in the human vascular endothelial cells. Although the DNA-binding sites for AP-1 were identified within the promoter regions of AGT, ACE and AT1R genes, RT-PCR and immunoblot assays indicated that AP-1 transactivation was only involved in AT1R upregulation, but did not affect the induction of AGT and ACE expression under the same conditions. Furthermore, ERKs and p38K functioned as the upstream protein kinases involving in AP-1 transactivation and AT1R upregulation under PM2.5 stimulation. In addition, the oxidative stress and proinflammatory responses in the PM2.5-treated vascular endothelial cells were significantly reduced when MAPKs and AP-1 activation were inhibited. Therefore, we conclude that PM2.5 exposure induces MAPK/AP-1 cascade activation, which contributes to AT1R upregulation and vascular endothelial dysfunction. Identifying novel therapeutic targets to alleviate AP-1 transactivation and restore AT1R expression may be helpful for the management of PM2.5-induced CV burden.


Assuntos
Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Material Particulado/toxicidade , Receptor Tipo 1 de Angiotensina/genética , Fator de Transcrição AP-1/genética , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Adesão Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Sistema de Sinalização das MAP Quinases , Estresse Oxidativo/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Fator de Transcrição AP-1/metabolismo , Ativação Transcricional , Regulação para Cima
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