scholarly journals The role of obesity in the implementation of genetic predisposition to the development of essential hypertension in men

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.


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.



2003 ◽  
Vol 33 (7) ◽  
pp. 1185-1192 ◽  
Author(s):  
SIMON HATCHER ◽  
ALLAN HOUSE

Background. The role of stress in the onset of chronic fatigue syndrome is unclear. Our objectives in this study were first, to determine the relation between the onset of chronic fatigue syndrome and stressful life events and difficulties. Secondly, we examined the role of a particular type of problem, dilemmas, in the onset of chronic fatigue syndrome.Method. We used a case–control design with 64 consecutive referrals from an Infectious Diseases/Liaison Psychiatry Fatigue clinic and 64 age- and sex-matched controls from a general practice population control group in Leeds. We had two main outcome measures; the odds ratios of the risk of developing chronic fatigue syndrome after experiencing a severe life event, severe difficulties or both in the year and 3 months preceding onset; and the proportion of subjects in each group who experienced a dilemma prior to onset.Results. Patients with chronic fatigue syndrome were more likely to experience severe events and difficulties in the 3 months (OR=9, 95% CI 3·2 to 25·1) and year (OR=4·3, 95% CI 1·8 to 10·2) prior to onset of their illness than population controls. In the 3 months prior to onset 19 of the 64 patients (30%) experienced a dilemma compared to none of the controls.Conclusions. Chronic fatigue syndrome is associated with stressful events and difficulties prior to onset. Those events and difficulties characterized as being dilemmas seem to be particularly important.



2008 ◽  
Vol 55 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Noriko AOI ◽  
Tomohiro NAKAYAMA ◽  
Naoyuki SATO ◽  
Kotoko KOSUGE ◽  
Akira HAKETA ◽  
...  


2020 ◽  
Vol 17 (3) ◽  
Author(s):  
Mahsa Rahnama ◽  
Qasem Asgari ◽  
Peiman Petramfar ◽  
Davod Tasa ◽  
Vahid Hemati ◽  
...  

Background: Toxoplasmosis is a common parasitic disease, which leads to serious disease symptoms in immunocompromised hosts and infants. Recent epidemiologic surveys showed that microbial agents may be associated with some cases of multiple sclerosis (MS). Objectives: This case-control study aimed to examine the role of Toxoplasma gondii in MS by evaluating sero-frequency of anti-T. gondii IgG (ATXAb) antibody between patients with MS and ordinary people in Shiraz Province, south of Iran during 2016 - 2018. Methods: Serum samples obtained from MS patients (n = 130), and a group of age and gender-matched controls (n = 130) with the same socioeconomic status with the patients’ group were collected to evaluate the prevalence of T. gondii IgG antibodies (ATXAb). Moreover, the presence of the ATXAb antibody of the patients and controls was determined by the ELISA test. SPSS 20 software was used to perform the statistical analysis (SPSS, inc., Chicago, USA). Results: Out of 130 (35.4%) cases with MS and 130 (13.8%) controls, 46 and 18 subjects were seropositive for ATXAb, respectively. Based on the chi-square test, a significant difference was observed in terms of the positivity rates of ATXAb between the MS patient group and the control group (P = 0.001). The mean ± standard deviation ATXAb levels in controls and MS patients were found to be 61 ± 34 and 114 ± 47 IU/mL, respectively. Also, there were statistically significant differences between the levels of these two groups (P = 0.001). Conclusions: Given the relationship between toxoplasmosis and MS, it is possible that the prevalence of MS decreases by increasing hygiene and preventing toxoplasmosis.



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.



2020 ◽  
Author(s):  
Salma Ahi ◽  
Mohammad Reza Dehdar ◽  
Naser Hatami

Abstract Objectives: Although in many studies, the relationship between autoimmune hypothyroidism (Hashimoto) and Vitamin D deficiency was shown, no research has been performed on the role of vitamin D in non-autoimmune hypothyroidism. Design: This was a Retrospective case–control study in Endocrinology clinic of Jahrom (south of Iran). The patients with Hashimoto (n=633) and non-Hashimoto hypothyroidism (n=305), along with a control group (n=200) were evaluated. 25(OH)D level, T3 and T4 levels were studied and Anti TPO and Anti TG tests were performed. The results of vitamin D level were analyzed and interpreted using SPSS in terms of the cause of hypothyroidism (immune and non-immune). Results: The results of the study showed a significantly lower level of vitamin D in both immune and non-immune Hashimoto’s thyroiditis (HT) in comparison to healthy controls (P<0.05). We observed a significant inverse correlation between the vitamin D and TGAb level (p=0.001, r=-0.261) and a direct correlation of vitamin D with TSH level (p=0.008, r=0.108) in HT patients. Conclusion: Finally, the results indicated that non-autoimmune hypothyroidism, as well as HT, is associated with vitamin D deficiency. The role of vitamin D deficiency in HT was thought to be in the association of higher autoantibody (TGAb) level; while, there should be further studies determining vitamin D deficiency's role in non-immune hypothyroidism.



1999 ◽  
Vol 181 (6) ◽  
pp. 1934-1938 ◽  
Author(s):  
Chung-Dar Lu ◽  
Ahmed T. Abdelal

ABSTRACT The ast operon, encoding enzymes of the arginine succinyltransferase (AST) pathway, was cloned from Salmonella typhimurium, and the nucleotide sequence for the upstream flanking region was determined. The control region contains several regulatory consensus sequences, including binding sites for NtrC, cyclic AMP receptor protein (CRP), and ArgR. The results of DNase I footprintings and gel retardation experiments confirm binding of these regulatory proteins to the identified sites. Exogenous arginine induced AST under nitrogen-limiting conditions, and this induction was abolished in an argR derivative. AST was also induced under carbon starvation conditions; this induction required functional CRP as well as functional ArgR. The combined data are consistent with the hypothesis that binding of one or more ArgR molecules to a region between the upstream binding sites for NtrC and CRP and two putative promoters plays a pivotal role in modulating expression of theast operon in response to nitrogen or carbon limitation.



2021 ◽  
Vol 28 (4) ◽  
pp. 489-495
Author(s):  
Krasimir Kostov ◽  
Alexander Blazhev

The role of endothelin-1 (ET-1) in the pathogenesis of hypertension (HTN) is not clearly established. There is evidence that its circulating levels are elevated in some forms of experimental and human HTN, but this was not a consistent finding. Based on these controversial data, we tested serum levels of ET-1 and Big ET-1 (the precursor of ET-1) in patients with essential HTN, comparing the results with those of healthy normotensive controls. The levels of ET-1 and Big ET-1 were measured by ELISA. Our results in patients with essential HTN showed that the mean levels of ET-1 (5.01 ± 2.1 pg/mL) were significantly higher (F = 6.34, p = 0.0144) than the mean levels in the control group (3.2 ± 1.0 pg/mL). The levels of Big ET-1 in patients with essential HTN (0.377 ± 0.1 pmol/L) were similar to those in the control group (0.378 ± 0.07 pmol/L) and did not differ significantly (F = 0.00, p = 0.9531). These data suggest that ET-1, but not Big ET-1, may play an important role in the pathogenesis of primary HTN.



2021 ◽  
Author(s):  
Hanife Tuba Akcam ◽  
Ozcan Erel

Abstract Purpose The role of oxidative stress in the pathogenesis of pterygium is still unclear. However, abnormal thiol disulfide homeostasis levels are involved in the pathogenesis of various systemic or ocular diseases. We aim to analyze dynamic thiol disulphide homeostasis in patients suffering from conjunctival pterygium using a contemporary technique. Methods Thirty-eight subjects suffering from pterygium and 35 age-gender matched healthy volunteers were recruited for study. For each case, total thiol, disulfide and native thiol levels in blood were obtained. Additionally, ratio of disulfide over total thiol, native thiol over total thiol and disulfide over native thiol were computed. Results The level of median native thiol was lower in pterygium group (318.2 µmol /L vs 333.4 µmol /L) and median disulfide was slightly higher in pterygium group (24.3 µmol /L vs 22.8 µmol /L) compared to control group. Both disulfide over total thiol and disulfide over native thiol ratios were higher in pterygium group, ratio of native thiol over total thiol was found to be higher in control group. Nevertheless, none of those differences were statistically significant at 95% confidence level. Notably, correlation test pointed to a negative correlation both between pterygium grade and native thiol and between total thiol and pterygium grade in pterygium group (P = 0.03 and 0.02 respectively). Conclusion A negative correlation hinting that slightly weakened dynamic thiol disulphide homeostasis in subjects with pterygium, a local ocular disease. Further studies with larger sample sizes may shed light on this potential relationship and justify systemic antioxidant therapies in these cases.



Sign in / Sign up

Export Citation Format

Share Document