scholarly journals Gene-environment interactions between polymorphic loci of MMPs and obesity in essential hypertension in women.

Author(s):  
Maria Ivanovna Moskalenko ◽  
Alexey Valerevich Polonikov ◽  
Inna Nikolaevna Sorokina ◽  
Tatyana Igorevna Yakunchenko ◽  
Yevgeniy Nikolayevich Krikun ◽  
...  

Backgraund: The prevalence of essential hypertension (ЕH) is increasing every year, both in Russia and around the world. Genetic and environmental risk factors are involved in the development of hypertension, and obesity plays an important role. Therefore, the study of gene-ecological interactions in the development of hypertension seems to be relevant. Aims: to study the gene-environment interactions between polymorphic loci of MMP and obesity in essential hypertension in women. Materials and methods: The study was conducted in a case-control design. The sample included 584 subjects: 375 patients with EH and 209 women in the control group. All individuals included in the study were genotyped for eight polymorphic loci of MMPs. Statistical data processing was performed using the software "STATISTICA". The study of the gene-environmental interactions during the formation of hypertension was performed using the GMDR method (Generalized Multifactor Dimensionality Reduction, http://www.ssg.uab.edu/gmdr). Results: rs11568818 MMР7 and rs11225395 MMР8 polymorphic loci were found to be involved in the development of arterial hypertension in women without obesity (p0,050). Fifteen three-, four-, and five-factor models of gene-environmental interactions of 8 MMPs with obesity, associated with EH (p=0,001), were found. It is shown that the analyzed SNPs are located in the DNA regions that bind to histones, marking promoters and enhancers, in the region of hypersensitivity to DNAse-1, in the binding sites of regulatory proteins and transcription factors. The loci of MMPs rs17577, rs11568818, rs1320632 and rs11225395 have cis-eQTL-value. They affecting the expression of the genes of MMP7, SNX21, SLC12A5 and RP11-817J15.3. Conclusions: SNP rs11568818 MMP7 and rs11225395 MMP8 and gene-environmental interactions of MMPs rs1799750, rs243865, rs3025058, rs11568818, rs1320632, rs11225395, rs17577, rs652438 with obesity are involved in the development of essential hypertension in women.


2020 ◽  
Vol 16 (4) ◽  
pp. 66-72
Author(s):  
Maria I. Moskalenko ◽  
Irina V. Ponomarenko ◽  
Alexey V. Polonikov ◽  
Inna N. Sorokina ◽  
Irina V. Batlutskaya ◽  
...  

BACKGROUND: Obesity is considered a non-infectious pandemic, and the increase in its spread is a serious medical and social problem. High values of body mass index closely correlate with arterial hypertension and its complications, but the effect of obesity on the realization of hereditary susceptibility to essential hypertension (EH) remains poorly understood. AIMS: To study the associations of polymorphic loci of MMPs with the development of EH in men depending on the presence of obesity. MATERIALS AND METHODS: The study was conducted in a case-control design. Surveyed 821 men 564 patients with hypertension and 257 patients of the control group. Groups of patients and controls were divided into subgroups depending on the presence of obesity. All men were genotyped for eight polymorphic loci of MMPs. Nonsynonymous SNPs were detected using the software SIFT (https://sift.bii.a-star.edu.sg/). The regulatory potential was studied using the HaploReg service (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php). The association of SNPs with the expression level was detected using GTEx-portal (http://www.gtexportal.org). RESULTS: It was found that in obese men allele A (OR=2.01; p=0.01) and genotype GG (OR=0.42, p=0.01) of rs11568818 MMP7 are associated with the essential hypertension. In men without obesity allele 6A (OR=1.32; p=0.04) of rs3025058 MMР3 and genotypes GG (OR=1.52; p=0.04) and GA (OR=0.63; p=0.03)) of rs17577 MMP9 are associated with the development of the disease. These SNPs located in region of promoter and enhancer histone marks, in the region of hypersensitivity to DNAse-1, in binding sites of regulatory proteins and transcription factors. These SNPs associated with the level of gene expression. CONCLUSIONS: In this study we established associations with the development of EH of SNP rs11568818 MMP7 in obese men and of SNPs rs3025058 MMР3 and rs17577 MMP9 in non-obese men.



Kardiologiia ◽  
2019 ◽  
Vol 59 (7S) ◽  
pp. 31-39 ◽  
Author(s):  
M. I. Moskalenko ◽  
S. N. Milanova ◽  
I. V. Ponomarenko ◽  
A. V. Polonikov ◽  
M. I. Churnosov

The aim of research. To study the association of polymorphic loci of matrix metalloproteinases with the development of essential hypertension (EH) in men of the Central Chernozem Region of Russia. Materials and methods. A study of 564 men with EH and 257 control men was performed. Analysis of the polymorphic loci of metalloproteinases rs11568818 MMР7, rs1320632 MMР8, rs11225395 MMР8, rs1799750 MMР1, rs3025058 MMР3 was performed using real-time PCR. The study of associations of SNPs and their haplotypes with the development of arterial hypertension was carried out using logistic regression analysis in the PLINK software (v. 2.050). The regulatory potential of polymorphic loci was analyzed in the HaploReg software (v. 4.1) (http://archive.broadinstitute.org). The effect of SNP on gene expression was studied using the data of the Genotype-Tissue Expression project (http://www.gtexportal.org/). Results. Haplotype including rs11568818 MMP7, rs1320632 MMP8, rs11225395 MMP8 and rs1799750 MMP1 associated with a high risk of disease in men (OR=2,58, pperm=0,04). These polymorphisms located in region of promoter and enhancer histone marks and in the region of hypersensitivity to DNAse-1. They located in sites of proteins bound (TBP, CJUN, CFOS and GATA2) and they associated with the level of gene expression ММР7, ММР27 and RP11-817J15.3 (in peripheral blood, skeletal muscles, nervous tissue and other). Сonclusion. Haplotype G-A-C-1G for polymorphisms rs11568818 MMP7, rs1320632 MMP8, rs11225395 MMP8, rs1799750 MMP1 are associated with the development of essential hypertension in men in the Central Chernozem Region of Russia.



INFO ARTHA ◽  
2017 ◽  
Vol 2 ◽  
pp. 56-79
Author(s):  
NFN Khusnaini ◽  
Agung Widi Hatmoko

Attitudes towards tax compliance (willingness to comply) Indonesian society is still low. Required an innovative tax dissemination to increase it. The purpose of this study was to determine whether the tax dissemination based on Fogg Behavioral Model (FBM) approach may increase wiliingness to comply. The FBM based tax dissemination asserts that for a person to perform a target behavior, which is a willingness to comply, he or she must be sufficiently motivated, have the ability to perform the behavior, and be trigerred, to perform the behavior. This research is a combination of qualitative and quantitative analysis of statistical data results of the questionnaire, interviews, and observations of the respondent and the experimental process of dissemination. The method used in this study is a quasi experimental with patterns of nonequivalent control group (pretest-post which is not equivalent). Based on the results of data analysis, interviews and observations of the respondent and the experiment, this research showed that theFBMbasedtaxdissemination hasapositiveimpactto willingnesstocomplyofthetaxpayers. 



2018 ◽  
Vol 69 (6) ◽  
pp. 1550-1553
Author(s):  
Rosana Manea ◽  
Bianca Elena Popovici ◽  
Carmen Daniela Neculoiu ◽  
Dan Minea ◽  
Alina Calin

Hypertension is a major risk factor for progression of the atherosclerotic process and for developing of degenerative cardiovascular diseases in adulthood. The aim of this study is to evaluate how the measurement of carotid intima - media thickness for prediction of essential hypertension in children can be used.The study group included 81 children and the control group 61 children, all aged between 5 - 17 years and 11 months old, and admitted in Children Hospital Brasov in the period of 2009 � 2014. The study protocol included: BMI, blood pressure and Doppler echography of the common carotid artery for each group. Mean age of the patients from the study group was 13.67 years, 43.20 % girls and 56.80 % boys, while in the control group, the mean age was 14.07 years, 54.10% girls and 45.90 % boys. 70.37% of the children from the study group presented obesity, while in the control group 40.98% were obese. The IMTC study group ranged from 0.52 - 0.69 mm and the limits of the normotensive subjects were 0.32 -0.54 mm. In both groups the obese patients were found to have increased carotid artery intima-media, which means that IMTC was positively correlated with BMI (p=0.000001).It is necessary to identify diagnostic methods easily applicable for children, allowing involvement of the characteristics of the arterial wall in the degenerative pathological processes. Increased intima-media ratio is positively correlated with high values of blood pressure.



2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei-feng Yan ◽  
Yue Gao ◽  
Yi Zhang ◽  
Ying-kun Guo ◽  
Jin Wang ◽  
...  

Abstract Background Essential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR). Methods A total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters. Results PFR and PFR/EDV decreased from the control group, through HTN(T2DM −), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM −) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM −) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (β = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = − 0.756 ~ 0.795). Conclusions T2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.



1981 ◽  
Vol 61 (s7) ◽  
pp. 367s-368s ◽  
Author(s):  
A. Fernandez-Cruz ◽  
M. Luque Otero ◽  
L. Llorente Perez ◽  
C. Fernandez Pinilla ◽  
N. Martell Claros

1. Human leucocyte AB antigens were determined by means of a lymphocyte toxicity test in 84 patients with essential hypertension and in 1000 blood donors. 2. The prevalence of HLA B8 was 16.4% in hypertensive patients and 8.9% in controls (P = 0.07). 3. The prevalence of HLA B12 was 34.5% in hypertensive patients and 26.9% in the control group (N.S.). In WHO stage III hypertension HLA B12 was found in six out of 10 patients. 4. The prevalence of HLA B15 was 1.2% in hypertensive patients and 6.4% in controls (P &lt; 0.05). 5. In view of a previous report of HLA antigens in a Spanish diabetic population, this study does not support the suggestion of a genetic and possibly HLA-linked connection between essential hypertension and diabetes mellitus among the Spanish population. 6. A positive family history of hypertension tended to be more common in those patients with essential hypertension associated with HLA B8.



2002 ◽  
Vol 48 (12) ◽  
pp. 2131-2140 ◽  
Author(s):  
Chikh Bengra ◽  
Theodore E Mifflin ◽  
Yuri Khripin ◽  
Paolo Manunta ◽  
Scott M Williams ◽  
...  

Abstract Background: Human hypertension is a complex, multifactorial disease with a heritability of more than 30–50%. A genetic screening test based on analysis of multiple single-nucleotide polymorphisms (SNPs) to assess the likelihood of developing hypertension would be helpful for disease management. Methods: Tailed allele-specific primers were designed to amplify by PCR six biallelic SNP loci [three in G protein-coupled receptor kinase type 4 (GRK4): R65L, A142V, and A486V; two in angiotensinogen: −6G→A and M235T; and one in aldosterone synthase: −344C→T] associated with essential hypertension. PCRs of SNP loci were coupled (via a common sequence of 21 nucleotide tails) to incorporate Universal Amplifluor™ primers labeled with fluorescein or sulforhodamine in a homogeneous format. Use of Amplifluors in SNP PCRs produced labeled amplicons, the fluorescence of which was quantified by a microplate reader and then analyzed via an Excel macro to provide genotypes for all six SNP loci. Unique restriction endonucleases were identified for five SNP loci that could independently confirm homogeneous PCR results when needed. Results: We developed six homogeneous PCR assays that were set up, performed, and fluorometrically analyzed in 96-well microplates. Allele frequencies were determined for six SNPs in 60 Italian hypertensive patients and a control group of 60 normotensive persons. A significant correlation (P = 0.034) between one SNP [GRK4 (A486V)] and the hypertensive patients was observed. Genotyping results for five of six SNPs were confirmed by digesting corresponding amplicons with locus-specific restriction endonucleases. Conclusions: We developed a simple and homogeneous fluorescent protocol that has been used to determine the SNP genotype for six loci in a population of hypertensive and normotensive persons. We also observed a significant association (P = 0.034) between one SNP (A486V) and an Italian population of mildly hypertensive patients.



2015 ◽  
Author(s):  
Javier Estrada ◽  
Teresa Ruiz-Herrero ◽  
Clarissa Scholes ◽  
Zeba Wunderlich ◽  
Angela DePace

DNA-binding proteins control many fundamental biological processes such as transcription, recombination and replication. A major goal is to decipher the role that DNA sequence plays in orchestrating the binding and activity of such regulatory proteins. To address this goal, it is useful to rationally design DNA sequences with desired numbers, affinities and arrangements of protein binding sites. However, removing binding sites from DNA is computationally non-trivial since one risks creating new sites in the process of deleting or moving others. Here we present an online binding site removal tool, SiteOut, that enables users to design arbitrary DNA sequences that entirely lack binding sites for factors of interest. SiteOut can also be used to delete sites from a specific sequence, or to introduce site-free spacers between functional sequences without creating new sites at the junctions. In combination with commercial DNA synthesis services, SiteOut provides a powerful and flexible platform for synthetic projects that interrogate regulatory DNA. Here we describe the algorithm and illustrate the ways in which SiteOut can be used; it is publicly available at https://depace.med.harvard.edu/siteout/



2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Fushun Zhang ◽  
Yuanyuan Zhang ◽  
Nan Jiang ◽  
Qiao Zhai ◽  
Juanjuan Hu ◽  
...  

Background. Some studies published previously have shown a strong correlation between hypertension and psychological nature including impulsion emotion or mindfulness and relaxation temperament, among which mindfulness and relaxation temperament might have a benign influence on blood pressure, ameliorating the hypertension. However, the conclusion was not confirmed. Objective. The meta-analysis was performed to investigate the influence of mindfulness and relaxation on essential hypertension interventions and confirm the effects. Methods. Systematic searches were conducted in common English and Chinese electronic databases (i.e., PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, PsycINFO, Cochrane Library, and Chinese Biomedical Literature Database) from 1980 to 2020. A meta-analysis including 5 studies was performed using Rev Man 5.4.1 software to estimate the influence of mindfulness and relaxation on blood pressure, ameliorating the hypertension. Publication bias and heterogeneity of samples were tested using a funnel plot. Studies were analyzed using either a random-effect model or a fixed-effect model. Results. All the 5 studies investigated the influence of mindfulness and relaxation on diastolic and systolic blood pressure, with total 205 participants in the control group and 204 in the intervention group. The random-effects model (REM) was used to calculate the pooled effect for mindfulness and relaxation on diastolic blood pressure (I2 = 0%, t2 = 0.000, P = 0.41 ). The random pooled effect size (MD) was 0.30 (95% CI = −0.81–1.42, P = 0.59 ). REM was used to calculate the pooled effect for mindfulness and relaxation on systolic blood pressure (I2 = 49%, t2 = 3.05, P = 0.10 ). The random pooled effect size (MD) was −1.05 (95% CI = −3.29–1.18, P = 0.36 ). The results of this meta-analysis were influenced by publication bias to some degree. Conclusion. All the results showed less influence of mindfulness and relaxation might act on diastolic or systolic blood pressure, when mindfulness and relaxation are used to intervene in treating CVD and hypertension.



2019 ◽  
Vol 2 (2) ◽  
pp. 13-19
Author(s):  
Neneng Maryani ◽  
Karin Nurseptiani

This research is based on field findings, namely low interest in learning Indonesian, lack of teacher initiative to use varied learning models that cause students to become bored in following the learning process in Indonesian subjects. The purpose of this study is to find out the increased interest in learning Indonesian by comparing the RADEC (Read, Answer, Discuss, Explain, and Create) learning models and conventional learning. The research method used was Nonequivalent Control Group Design with a population of 173 students, and two sample classes namely class V as an experimental class totaling 28 students and class VI as a control class totaling 37 students. From the results by statistical data using SPSS version 24.0 for windows after the data are declared normally distributed and come from homogeneous samples through normality and homogeneity tests, it is known that the results of hypothesis testing using the Compare Means test with Independent Samples Test obtained sig = 0,000. Because the significance <0.05, it can be concluded that Ho is rejected, which means "There is a difference in the increase in interest in learning Indonesian by using the RADEC learning model compared to using the conventional model in SD Negeri Sukamaju, Pagerageung District, Tasikmalaya District". The score is in the interval 66.4 -70.1. Based on this, it can be concluded that the implementation of the RADEC learning model is quite successful in increasing interest in learning Indonesian compared to using conventional models. Suggestions that can be recommended based on the findings of this study include expected to be able to develop RADEC learning models that are collaborated with other learning techniques as an innovation to increase learning interest.



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