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To determine the independent predictive role of nasal obstruction in resistant hypertension (RH) in uncontrolled hypertensive patients with obstructive sleep apnea (OSA).This prospective cohort study comprised of 236 OSA patients with uncontrolled blood pressure (BP) using 1 or 2 classes of antihypertensive drugs visiting Sleep Medicine Center from April 2021 to March 2022. Information on demographic characteristics, comorbidities, BP control and classes of antihypertensive medication, sleep-related symptoms, Nasal Obstruction Symptom Evaluation (NOSE) Scale and sleep parameters was collected. RH incidence according to the BP control and classes of antihypertensive drugs data during the 5 month follow-up was collected.After 5 month follow-up, 217 participants were included for final data analysis. Ninety-five subjects had nocturnal nasal obstruction with a higher proportion of RH (36.8% vs. 17.2%, p = 0.001) compared to those without nocturnal nasal obstruction. After adjustment for demographic characteristics, sleep-related symptoms and OSA severity, multinomial logistic regression models showed that nocturnal nasal obstruction (all ORs 2.5, p 0.05) or NOSE ≥ 8 (all ORs 4.5, p 0.05) was independently associated with a higher odds of RH. Nasal obstruction treatment improved NOSE score significantly, but did not reduce the incidence of RH significantly. Effective nasal obstruction treatment was associated with antihypertensive drugs reduction (OR 4.43; 95% CI 1.20-16.27).Nasal obstruction is an independent predictor of RH in uncontrolled hypertensive patients with OSA. In addition to the treatment of OSA, assessment and treatment of nasal obstruction should be considered in the management of uncontrolled hypertensive patients with OSA.

C1q-tumor necrosis factor-related protein-9 (CTRP9) is an important adipocytokine that is closely associated with cardiovascular disease. This study aimed to detect CTRP9 expression in hypertensive patients and mice and to analyze its effects on hypertension-related atherogenesis. First, circulating CTRP9 levels were detected in both nonhypertensive subjects and hypertensive patients. The results showed that plasma CTRP9 levels were increased in hypertension patients compared with control subjects and gradually elevated in the Grade I, Grade II, and Grade III groups. While nondipper state did not affect CTRP9 expression in hypertension patients. Hypertension patients with carotid atherosclerotic plaque (CAP) exhibited higher CTRP9 levels and the high CTRP9 group exhibited significantly higher CAP morbidity, CTRP9 levels were positively correlated with the occurrence of CAP. Then, effects of CTRP9 on angiotensin II (Ang II)-induced endothelial dysfunction were analyzed in vitro, and the results exhibited that treatment with Ang II significantly increased CTRP9 mRNA expression in endothelial cells (ECs), and downregulation of CTRP9 expression aggravated Ang II-induced endothelial dysfunction in ECs. Mice were infused with Ang II, and CTRP9 was also increased in Ang II-infused mice and mainly secreted by ECs. In Ang II-infused ApoE-/- mice, treatment with recombinant CTRP9 significantly reduced atherosclerotic area and alleviated endothelial dysfunction. In conclusion, our results may found that CTRP9 delayed the progression of hypertension-related arteriosclerosis by alleviating endothelial dysfunction.

Social engineering attacks have posed a serious security threat to cyberspace. However, there is much we have yet to know regarding what and how lead to the success of social engineering attacks. This paper proposes a conceptual model which provides an integrative and structural perspective to describe how social engineering attacks work. Three core entities (effect mechanism, human vulnerability and attack method) are identified to help the understanding of how social engineering attacks take effect. Then, beyond the familiar scope, we analyze and discuss the effect mechanisms involving 6 aspects (persuasion, social influence, cognition & attitude & behavior, trust and deception, language & thought & decision, emotion and decision-making) and the human vulnerabilities involving 6 aspects (cognition and knowledge, behavior and habit, emotions and feelings, human nature, personality traits, individual characters), respectively. Finally, 16 social engineering attack scenarios (including 13 attack methods) are presented to illustrate how these mechanisms, vulnerabilities and attack methods are used to explain the success of social engineering attacks. Besides, this paper offers lots of materials for security awareness training and future empirical research, and the model is also helpful to develop a domain ontology of social engineering in cybersecurity.

Myocardial hypertrophy is an important cause of heart failure and sudden death. Studies have shown that Mitofusin-2 (MFN2) is downregulated in myocardial hypertrophy, but the upstream regulation mechanism underlying its downexpression in cardiomyocytes is still unclear. This study aims to identify the expression profile of microRNAs (miRNAs) in hypertrophic cardiomyopathy (HCM) and explore the function of miRNA-20 in inducing cardiomyocyte hypertrophy through regulating MFN2. Through miRNA + mRNA microarray analysis, 1451 miRNAs were identified, 367 miRNAs expressed differently between groups. Meanwhile, a number of 24,718 mRNAs were identified, among which 5850 mRNAs were upregulated and 3005 mRNAs were downregulated in HCM group compared with the control group. Expression of hsa-miRNA-20a-5p was 2.26 times higher in the HCM group compared with the control group and 7 target gene prediction programs predicted MFN2 as a target of miRNA-20. In vitro model of hypertrophic cardiomyocytes displayed high expression level of miRNA-20, atrial natriuretic peptide (ANP) mRNA, and protein, accompanying low expression level of Mfn2 mRNA and protein, which meant miRNA-20 played a role in cardiomyocyte hypertrophy and might interact with MFN2 to function. Thereafter, overexpression of miRNA-20 led to cell hypertrophy accompanied with lowly expressed Mfn2 mRNA and protein. When transfected with miRNA-20 inhibitors, the expression of miRNA-20 and ANP gene was attenuated and MFN2 was the other way around. The cell surface area of Ang II group and mimic group was significantly larger compared with the control group, and in the inhibitor+Ang II group, the area was significantly decreased compared with the Ang II group. Dual-luciferase assays showed that miRNA-20 bound to 3' untranslated region of MFN2 and inhibited its expression. In conclusion, hypertrophic myocardium and normal myocardium have different miRNA expression profiles and the effect of miRNA-20 reducing the expression of MFN2 plays a role in promoting cardiomyocyte hypertrophy.

Background: Essential hypertension (EH) is a chronic disease of universal high prevalence and a well-established independent risk factor for cardiovascular and cerebrovascular events. The regulation of blood pressure is crucial for improving life quality and prognoses in patients with EH. Therefore, it is of important clinical significance to develop prediction models to recognize individuals with high risk for EH. Methods: In total, 965 subjects were recruited. Clinical parameters and genetic information, namely EH related SNPs were collected for each individual. Traditional statistic methods such as t-test, chi-square test and multi-variable logistic regression were applied to analyze baseline information. A machine learning method, mainly support vector machine (SVM), was adopted for the development of the present prediction models for EH. Results: Two models were constructed for prediction of systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. The model for SBP consists of 6 environmental factors (age, BMI, waist circumference, exercise [times per week], parental history of hypertension [either or both]) and 1 SNP (rs7305099); model for DBP consists of 6 environmental factors (weight, drinking, exercise [times per week], TG, parental history of hypertension [either and both]) and 3 SNPs (rs5193, rs7305099, rs3889728). AUC are 0.673 and 0.817 for SBP and DBP model, respectively. Conclusions: The present study identified environmental and genetic risk factors for EH in northern Han Chinese population and constructed prediction models for SBP and DBP.

Background The ECE1 gene polymorphisms have been studied as a candidate gene in essential hypertension, but no consensus has been reached. To systematically explore their possible association, a case‒control study was conducted. Methods This study included 398 hypertensive subjects and 596 healthy volunteers as control subjects in the Northern Han Chinese. A total of 10 tag SNPs of ECE1 gene were genotyped successfully by TaqMan assay. Results A total of 10 SNPs (rs212544, rs2076280, rs115071, rs2076283, rs9426748, rs11590928, rs212515, rs2236847, rs2282715, and rs2774028) were identified as the tag SNPs for ECE1 gene. Although no positive connection has been found in general population, several SNPs have been found to be related to EH risk in gender‐stratified subgroup analysis. In males, rs115071 T allele influenced EH risk in a protective manner, with dominant model (TT+TC vs. CC: p = .032, OR = 0.655, 95% CI = 0.445–0.965), additive model (TT vs. TC vs. CC: p = .019, OR = 0.616, 95% CI = 0.411–0.924), as well as allele comparison (T vs. C: p = .045, OR = 0.702, 95% CI = 0.496–0.992). While, in females, rs212544 AA genotype would increase the onset risk of EH (recessive model: AA vs. GA+GG, p = .024, OR = 1.847, 95% CI = 1.086–3.142). In the three haplotype blocks identified, rs2076283‐rs2236847 C‐T haplotype was associated with a decreased risk of EH (OR = 0.558, p = .046). Conclusion The current case‒control study suggested that several SNPs and related haplotypes on ECE1 gene might be associated with the susceptibility of EH in certain gender subgroups in the Northern Han Chinese population., The current study suggested that several SNPs and related haplotypes on ECE1 gene might be associated with the susceptibility of EH, which providing evidences to the early prevention, risk assessment, and individualized therapy of EH to some extent.

Hypertension, a multifactorial disease, is a major risk factor for the development of stroke, coronary artery disease, heart failure, and chronic renal failure. However, its underlying cellular and molecular mechanisms remain largely elusive. Numerous studies have shown that microRNAs (miRNAs) are involved in a variety of cellular processes, including cellular proliferation, apoptosis, differentiation, and the development of diseases. microRNA-21 (miR-21), a conserved single-stranded non-coding RNA that is composed of approximately 22 nucleotides, is one of the most intensively studied miRNAs in recent years, and it can regulate gene expression at the post-transcriptional level. miR-21 is expressed in many kinds of tumors and in the cardiovascular system, and it plays an important role in the occurrence and development of cardiovascular diseases. In recent years, more and more evidence indicates that miR-21 plays an important role in hypertension. This article reviews the source, function, and altered levels of miR-21 in hypertension and the role of miR-21 in the pathogenesis of hypertension and target organ damage (TOD). The potential role of miR-21 as a new target for predicting and treating hypertension is also explored.

Mitofusin 2 (Mfn2), a gene that negatively regulates the proliferation of vascular smooth muscle cells (VSMCs), is expressed at low levels in the VSMCs of hypertensive patients. DNA methylation can inhibit gene expression. The purpose of this study was to investigate the relationship between Mfn2 methylation and essential hypertension (EH). After bioinformatics analysis, five EH patients and five normal control (NC) subjects were selected for methylation chip screening. Then, bisulfite DNA sequencing was used to analyze the methylation status of differentially methylated fragments of Mfn2 in 40 EH patients and 36 NC subjects. Mfn2 mRNA expression in the blood was detected by RT-qPCR. There were three CpG islands in the full length Mfn2 DNA sequence and some transcription factor binding sites in these regions, including Sp1, Ap2, GATA box, NF-κB, etc. The chip screening showed that only the third CpG island had a significantly high degree of methylation. Subsequent verification experiments found that the EH group had a significantly lower C base rate of methylation than the NC group (2.5% vs. 44.44%, P 0.0001), but a similar CpG methylation rate (P 0.05). RT-qPCR detection showed that the level of Mfn2 mRNA expression was significantly lower in the EH group than in the NC group (P = 0.013). Further association analysis showed that the level of Mfn2 methylation was associated with systolic blood pressure and diastolic blood pressure (r = -0.902, r = -0.713, respectively) but not the other indexes. The DNA methylation level of Mfn2 was significantly lower in hypertensive patients than in control subjects, which may be an independent risk factor for EH.

Myocardial hypertrophy is an important cause of heart failure and sudden death. Studies have shown that Mitofusin-2 (

Human cytomegalovirus (HCMV) has been reported to be highly expressed in essential hypertension (EH), and it has been proposed that HCMV infection may contribute to EH development. However, different studies showed opposite results. The present meta-analysis was performed to investigate the association between HCMV infection and the risk of EH. All relevant literature from 1980 to 2015 was extracted from six electronic databases. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of the association of HCMV infection and risk of EH. Sensitivity analysis and examination for bias were conducted to evaluate cumulative evidence of the association. The random-effect model using the Mantel-Haenszel method was used to give the individual effect-size estimates. Of the 11,878 participants included in this study, there were 3,864 EH patients and 8,014 control subjects. Meta-analysis of nine studies performed in a random-effect model found that EH patients had a higher risk of HCMV infection than normal control subjects (OR = 1.47, 95%CI: 1.13-1.90, P = 0.004; heterogeneity: I(2) = 66%, P = 0.002). Sensitivity analysis and bias examination showed the overall quality and consistency of the studies to be acceptable. For subgroup analysis, studies of Chinese populations were selected for further analysis. There was a significant association between HCMV infection and EH among Chinese patients (OR = 2.18, 95%CI:1.43-3.31, P = 0.0003) but not among other ethnic groups (OR = 1.11, 95%CI:0.95-1.31, P = 0.19). These findings provide quantitative support for the association between HCMV infection and high risk of EH in individuals of Chinese ethnicity.

The present study was to investigate the role of bradykinin receptors genes polymorphisms on hypertension risk in Northern Han Chinese population. We also carried out a meta-analysis on Chinese to derive a more full assessment of this association.A total of 976 subjects from Northern Han Chinese and 7 studies with 1599 cases and 1425 controls were included in this case-control study and in the current meta-analysis, respectively. For the case-control study, we identified the genotypes of -58T/C and 1098A/G polymorphism in BDKRB2 and BDKRB1 genes, respectively, by TaqMan PCR method. Overall, we found significant association between the -58T/C polymorphism and the increased risk of hypertension in the allele comparison (p = 0.01, OR = 1.386, 95% CI [1.138-1.688]). Subgroup analysis by gender suggested that this obvious association could still be found in males, but not in females. For the 1098A/G polymorphism, no significant association was revealed in overall and subgroup analysis. For the meta-analysis involving the -58T/C polymorphism, a significant association between this polymorphism and hypertension was observed in the whole group. In Chinese Han subgroup, we found significant association with hypertension in allele comparison(C vs. T: p = 0.03, OR = 1.28, 95% CI 1.03-1.59, pheterogeneity = 0.05).Our case-control study indicated that -58T/C might be significantly associated with the increased risk of hypertension in Northern Han Chinese population, which was partially confirmed by our meta-analysis.

Our aim was to compare direct stenting (DS) with conventional stenting (CS) in patients with acute coronary syndrome (ACS). We searched PubMed, EMBASE, and ISI web of science for eligible studies. Primary end point was major adverse cardiac events (MACEs) in short term. Secondary end points were 1-year mortality and after-procedural no-reflow phenomenon. Twelve trials in 8998 patients were included. The odds ratios (ORs) were pooled using the Mantel-Haenszel fixed effect model. Short-term MACEs were significantly reduced in the DS arm in contrast to the CS (5.00% vs 8.08%, DS vs CS, respectively, OR [95% confidence interval] = 0.61 [0.46-0.80], P = .0004). One-year mortality and after-procedural no-reflow phenomenon were significantly lower in the DS group. No heterogeneity was observed through I2 test ( Phet = .81, .89, and .77 for each end point, respectively). This meta-analysis demonstrated that in selected patients with ACS, DS is not only safe and feasible but also reduces short-term and 1-year mortality as well as the occurrence of after-procedural no-reflow phenomenon.

Single nucleotide polymorphisms (SNPs) within a β-adrenergic receptor (ADRB2) were shown to be related to lipid traits or hyperlipidemia in different ethnicities, but not in a Chinese population. We performed the present study to investigate the possible relationship between them in a Chinese hypertensive population. Seven hundred and eighty-three hypertensive subjects were enrolled in the hospital-based retrospective research. Using the TaqMan PCR method, three polymorphisms (C-47T, A46G, and C79G) of ADRB2 were detected. For the whole population, no significant statistical difference was found for all serum lipids. Similar findings were seen in men and women subgroups. Subsequently, in the case-control study, we observed that the A46G polymorphism was significantly associated with the elevated risk of hypertriglyceridemia in the dominant model (OR: 1.47, 95%CI: 1.05-2.06, P = 0.025). There are no significant differences in the other four models. With regard to C79G and C-47T, no significant association was seen in this population. In addition, haplotype analysis showed that the TAC haplotype carrying frequent alleles of the three SNPs played a reduced role in hypertriglyceridemia risk and the TGC haplotype carrying rare allele of A46G expressed a significant risk effect. In conclusion, these findings indicated that the ADRB2 SNPs might be a genetic risk factor for dyslipidemia in the Chinese hypertensive patients.

The β1-adrenoceptor (ADRB1) gene Arg389Gly polymorphism has been extensively studied as a candidate gene in essential hypertension (EH), but no consensus has been reached on the relationship between this polymorphism and EH risk. To systematically explore their possible association, a meta-analysis was conducted. All relevant case-control trials in English-language publications before 1 June 2012 were identified by searching the PubMed and Embase databases. Finally, eight articles met our inclusion criteria, including a total of 5,088 patients with EH and 6,515 controls. No evidence of publication bias was found. Fixed-effects model and random-effects model were applied for dichotomous outcomes to combine results from individual studies. Overall, the Gly allelic frequency of Arg389Gly polymorphism was significantly lower in EH subjects than that in controls (Gly versus Arg: P = 0.04, OR = 0.89, 95 % CI [0.80-1.00], P heterogeneity = 0.03, I (2) = 52 %, random-effects model; GlyGly + ArgGly versus ArgArg: P = 0.02, OR = 0.86, 95 % CI [0.76-0.97], P heterogeneity = 0.08 and I (2) = 42 %, random-effect model). Subgroup analysis by ethnicity detected this association only in East Asians. In sensitivity analysis, the study by Bengtsson K was recognized as the main cause of heterogeneity, which was the only one study with the diagnostic standard for EH as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg. We concluded that the Gly allele of ADRB1 Arg389Gly polymorphism might confer lower risk for EH, especially in East Asians.

Background Left ventricular hypotrophy (LVH) is very common in hypertensives even after antihypertensive treatment. Mitofusin 2 (Mfn2) is a critical negative regulator of vascular smooth muscle cell (VSMC) hypertrophy by regulating mitochondrial fusion, ras/raf/MEK signal pathway, et al. The purpose of this study was to investigate whether candesartan attenuated cardiac remodeling by improving expression and function of mitofusin 2 in SHR. Methods Nine weeks old spontaneously hypertensive rats (SHR) were selected and treated with candesartan for eight weeks. Then, heart tissues were investigated for signs of cardiac remodeling, mitochondrial structure and membrane potential, mitochondrial enzyme activities, hydrogen peroxide, mRNA and protein expression of Mfn2/ras/raf/MEK signaling pathway in heart tissues. Results The results showed that cardiac remodeling was obviously in SHR group: cardiac cell alignment was irregular; cardiac fibers became thick, irregular and enlarged; cell density was reduced in SHR compared to WKY. After candesartan treatment, histopathological structure improved significantly which were consistent with mitochondrial morphology, mitochondrial membrane potential, mitochondrial enzyme activities, hydrogen peroxide, Mfn2/ras/raf/MEK gene and protein expression in cardiac tissues. What's more, although blood pressure was well controlled in a normal range, cardiac remodeling wasn't avoided. In general, candesartan obviously repressed cardiac hypertrophy and cardiac remodeling significantly compared to SHR untreated group, but didn't reverse it. Conclusions Mfn2 is negatively associated with cardiac remodeling. Candesartan treatment can improve mitochondrial structure and function and regulate Mfn2/ras/raf/MEK signaling pathway. Mfn2 may be used a potential marker for cardiac remodeling and a novel therapeutic target for target organ damage protection.

To investigate the relationship between the Trp64Arg polymorphism of β3-adrenergic receptor (ADRB3) gene and obesity and the levels of blood lipids in the Northern Han Chinese population.A total of 1 602 subjects in northern Han Chinese were recruited in this study, including 995 males and 607 females. Genotyping was performed using the TaqMan assay to identify the Trp64Arg polymorphisms of the ADRB3. The relationship between the polymorphism and obesity and blood lipids was analyzed.The genotype distribution for Trp64Arg polymorphism was in conformity with the Hardy-Weinberg equilibrium (HWE) in the recruited population (χ² = 0.043, P = 0.087). The frequency of Arg64 allele was 15.82%. In the overall analysis, no significant association was showed between the Trp64Arg polymorphism and the Body Mass Index (BMI) or the levels of blood lipids. Subgroup analysis was performed by hypertension. In the hypertensive subgroup, the results showed significant association between the polymorphism and the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and the ratio of TC and high-density lipoprotein cholesterol (TC/HDL-C) (TC: (5.27 ± 1.04) mmol/L vs (5.10 ± 1.02) mmol/L, t = 2.334, P = 0.02; LDL-C: (3.42 ± 0.88) mmol/L vs (3.27 ± 0.87) mmol/L, t = 2.067, P = 0.039; TC/HDL: 4.81 ± 1.31 vs 4.57 ± 1.25, t = 2.563, P = 0.011). Stepwise multiple regression analysis showed that there were significant associations between the Trp64Arg polymorphism and the levels of blood lipids. The polymorphism might affect 3.2% variances of the level of TC (P = 0.030, R² = 0.032), 2.5% variances of the level of LDL-C (P = 0.030, R² = 0.025), 3.4% variances of the TC/HDL-C ratio (P = 0.001, R² = 0.034), respectively. In the normatensive subgroup, there was no significant association between the polymorphism and the levels of lipids. No significant association was observed between the polymorphism and BMI either in the hypertension group or in the normotension group.The Trp64Arg polymorphism in ADRB3 gene may be associated with the levels of blood lipids of the Chinese Han patients with essential hypertension. The hypertensive patients with the Trp64Trp genotype may be liable to dyslipidemia.

No consensus has been reached on the association between the β2-adrenergic receptor polymorphisms A46G and C79G and essential hypertension risk. We performed a meta-analysis to confirm the possible association. After reviewing 303 reports in PubMed and 359 reports in Embase, we included in our meta-analysis 18 articles (20 studies) that met our inclusion criteria. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. There was no statistical association between A46G and hypertension risk in all subjects, Asians or Caucasians. However, an association was observed in the dominant genetic model (AA vs. (AG+GG)) (P=0.04, odds ratio (OR)=1.38, 95% confidence interval (CI) 1.01-1.87, P(heterogeneity)=0.98, fixed-effects model) in the subgroup of mixed Africans. No overall statistical association could be found between C79G and hypertension risk or any ethnic subgroup. In the research conducted on severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥95 mm Hg hypertensive population), significant association was found in the dominant genetic model (CC vs. (CG+GG)) (P=0.04, OR=1.38, 95% CI 1.02-1.86, P(heterogeneity)=0.03, random-effects model), and there was also a borderline significance between the C79 allele and severe hypertension (P=0.05, OR=1.26, 95% CI 1.00-1.57, P(heterogeneity)=0.04, random-effects model). No association could be found in this study between the two polymorphisms and stage 2 hypertension. More studies stratified for different ethnicities and different stages of hypertension should be performed in the future.

Background Hypertension is a leading global health threat and a major cardiovascular disease. Since clinical interventions are effective in delaying the disease progression from prehypertension to hypertension, diagnostic prediction models to identify patient populations at high risk for hypertension are imperative. Methods Both PubMed and Embase databases were searched for eligible reports of either prediction models or risk scores of hypertension. The study data were collected, including risk factors, statistic methods, characteristics of study design and participants, performance measurement, etc. Results From the searched literature, 26 studies reporting 48 prediction models were selected. Among them, 20 reports studied the established models using traditional risk factors, such as body mass index (BMI), age, smoking, blood pressure (BP) level, parental history of hypertension, and biochemical factors, whereas 6 reports used genetic risk score (GRS) as the prediction factor. AUC ranged from 0.64 to 0.97, and C-statistic ranged from 60% to 90%. Conclusions The traditional models are still the predominant risk prediction models for hypertension, but recently, more models have begun to incorporate genetic factors as part of their model predictors. However, these genetic predictors need to be well selected. The current reported models have acceptable to good discrimination and calibration ability, but whether the models can be applied in clinical practice still needs more validation and adjustment.

This study was designed to investigate the differences in the plasma proteome of healthy normotensive, prehypertensive, and hypertensive subjects. A case-control pilot study was conducted among well-matched subjects. Plasma protein was analyzed by two-dimensional electrophoresis combined with MALDI-TOF mass spectrometry. The results showed that there were 22 differentially expressed spots among the three groups, which corresponded to 18 proteins involved in inflammation and immunity, lipid metabolism, transport, coagulation and fibrinolysis, cell proliferation and apoptosis, and anti-oxidation. With an increase in blood pressure, these proteins were differentially expressed which indicated that prehypertension probably was an early stage of hypertension.

Human cytomegalovirus (HCMV) has been reported to be highly expressed in essential hypertension (EH), and it has been proposed that HCMV infection may contribute to EH development. However, different studies showed opposite results. The present meta-analysis was performed to investigate the association between HCMV infection and the risk of EH. All relevant literature from 1980 to 2015 was extracted from six electronic databases. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of the association of HCMV infection and risk of EH. Sensitivity analysis and examination for bias were conducted to evaluate cumulative evidence of the association. The random-effect model using the Mantel-Haenszel method was used to give the individual effect-size estimates. Of the 11,878 participants included in this study, there were 3,864 EH patients and 8,014 control subjects. Meta-analysis of nine studies performed in a random-effect model found that EH patients had a higher risk of HCMV infection than normal control subjects (OR = 1.47, 95%CI: 1.13-1.90, P = 0.004; heterogeneity: I(2) = 66%, P = 0.002). Sensitivity analysis and bias examination showed the overall quality and consistency of the studies to be acceptable. For subgroup analysis, studies of Chinese populations were selected for further analysis. There was a significant association between HCMV infection and EH among Chinese patients (OR = 2.18, 95%CI:1.43-3.31, P = 0.0003) but not among other ethnic groups (OR = 1.11, 95%CI:0.95-1.31, P = 0.19). These findings provide quantitative support for the association between HCMV infection and high risk of EH in individuals of Chinese ethnicity.

Mitofusin-2 (MFN2) is a mitochondrial protein associated with mitochondrial fusion process. It was initially identified as a hyperplasia suppressor and implicated in Charcot-Marie-Tooth disease. Recent studies showed that MFN2 played important roles in the development of multiple tumors. Here we examined MFN2 expression in 30 lung adenocarcinoma samples and revealed that the expression of MFN2 was significantly higher in lung adenocarcinoma tissues as compared to adjacent normal tissues. We then investigated the impact of MFN2 knockdown on A549 human lung adenocarcinoma cells and showed that cell proliferation, cell cycle and invasion behavior were all deregulated by MFN2 knockdown. And deregulation of cell cycle pathway after MFN2 knockdown was confirmed by microarray analysis. Furthermore, microarray analysis also revealed that different oncogenes such as RAP1A, RALB and ITGA2 were oppositely regulated by MFN2, which provided molecular clues for the paradoxical functions of MFN2 in tumor development. Taken together, our study unraveled the tumor-promoting functions of MFN2 in lung adenocarcinoma and implicated that the role of MFN2 in cancer development might be more complicated than expected and should be explored in detail in the future.

ever, these findings only partially explain EH. The Human Genome Project, the International HapMap Project, and the development of molecular genetics have sparked new interest in elucidating the genetic mechanisms underlying EH. However, although hundreds of hypertension-related genes have been identified and some genome-wide association studies (GWAS) have produced interesting results, only 1% of blood pressure (BP) changes can be explained by GWAS. 3–5 One prominent use of GWAS is to identify genetic variants associated with common diseases and complex traits. 6 However, these studies have not provided much information regarding the genetic mechanisms underlying EH. This may be because EH is a multifactor and multigenetic disease, and its progression is affected by many environmental and genetic factors. Typically, for any particular trait, the cumulative effects of multiple single nucleotide polymorphisms explain only a small fraction of each individual’s risk for the trait. Some scientists argue that the methods used for analysis are not necessarily reasonable, only common variants are detected in a given population (>5%), rare variants are untested, or gene-gene and gene-environment interactions are not estimated. 7 However, these may not be the key reasons why GWAS have failed in the study of EH. Other very important characteristics of GWAS relevant to such investigations are discussed below. First, the age of the individuals included in the normotensive and hypertensive groups used in previous

Nax , an α-subunit of the sodium channel encoded by the SCN7A gene, has been deemed to be a sensor of the concentration of sodium in the brain and may be involved in salt intake behavior. We inferred that Nax /SCN7A may participate in the regulation of blood pressure and the pathogenesis of essential hypertension (EH). The present case-control study involving 615 hypertensives and 617 normotensives was performed to investigate the association between SCN7A polymorphisms and EH in the Northern Han Chinese population. The three common single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the exons of SCN7A were genotyped with the TaqMan assay. Significant association between SNP rs7565062 and EH was found under the addictive and dominant genetic models (P = 0.024, OR = 1.283, 95%CI [1.033-1.592]; P = 0.013, OR = 1.203, 95%CI [1.040-1.392]; respectively). The three SNPs were in close pair-wise linkage disequilibrium with each other and the haplotype analyses indicated that haplotype G-A-T was significantly associated with increased risk of EH (P = 0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A was significantly associated with EH and the allele T of rs7565062 or the related haplotype G-A-T will be a genetic risk factor for EH in the Northern Han Chinese population.

Background: The G894T (rs1799983) polymorphism in endothelial nitric oxide synthase (eNOS/NOS3) gene has been implicated in susceptibility to essential hypertension (EH) in some studies, but no clear consensus has been reached in the Chinese population.This study aimed to investigate the association of the G894T polymorphism and EH in Han Chinese.First, a case-control study was performed involving 1525 subjects in northern Han Chinese to study the association between G894T variants and EH and then a meta-analysis was conducted of all available studies in Han Chinese. A total of 25 studies comprising 13,443 subjects were finally included in this meta-analysis.The present case-control study failed to show significant association of G894T variant with EH in northern Han Chinese. The subsequent meta-analysis showed that this polymorphism might be associated with EH in Han Chinese (p0.001, OR = 1.32), especially in southern Han Chinese (p0.001, OR = 1.59), but not in northern Han Chinese (p = 0.12, OR = 1.16). The meta-regression analysis suggested that the geographic difference of subjects was related to heterogeneity (p = 0.029).The relationship between the G894T polymorphism and hypertension in Han Chinese may be attributed to the difference in geographic background of subjects. It is necessary to carry out further research with a large sample size and focusing on gene-environment interactions.

Hypertension is one of the leading risk factors for mortality. The renin-angiotensin-aldosterone system (RAAS) is a potent and powerful mediator in the homeostasis of hypertension. Here, the association between six candidate genes, renin, adrenoceptor β3, angiotensinogen, aldosterone synthase, angiotensin II receptor type 1 and angiotensin II receptor type 2, that are related to RAAS and essential hypertension (EH) was evaluated and explored in northern Chinese Han individuals. A case-control study including 1090 EH cases and 700 controls was performed. Eight single-nucleotide polymorphisms (SNPs), rs699, rs4762, rs5707, rs5186, rs4994, rs1799998, rs5193 and rs5194, located in the six genes were genotyped with TaqMan real-time PCR method. Statistical analysis software (SPSS 17.0) was used for descriptive statistics and association analyses. Among the six genes related to RAAS, the frequencies of rs4994 (ADRB3) and rs5194 (AGTR2) were found to be significantly different between the EH cases and controls (P0.05). Logistic regression analyses adjusted for covariates showed rs4994 to be closely associated with EH under the recessive (P = 0.019, odds ratio (OR) = 0.373, 95% confidence interval (CI) 0.163-0.851) and homozygous (P = 0.028, OR = 0.394, 95% CI 0.172-0.903) models. The association was also significantly close in the male subset (P0.05). Significant association was also observed between rs1799998 (CYP11B2) and EH (P0.05) in the dominant, additive and allelic models. These data demonstrated that ADRB3 rs4994 and CYP11B2 rs1799998 were significantly closely associated with EH in northern Han Chinese individuals. The CC of rs4994 and CC or C allele of rs1799998 might be protective genetic factors of hypertension.

Essential hypertension (EH) is regarded as a multifactorial and poly- genic disease, and its underlying mecha- nism is very complex. A new model of EH pathogenesis was developed in the pres- ent work. This model is suitable for the study, diagnosis, treatment, and preven- tion of EH. It incorporates not only genetic and environmental factors, but also com- pensatory and time factors as the third and fourth types of factors that contribute to the development of EH. Compensatory factors are defined here as specific blood pressure (BP) regulators, the ability of the body to regulate BP, and the process of BP regulation. Time factors include the age of the patient and the duration of EH in that patient. Over time, genetic, environmental, compensatory, and time factors are dy- namic. In this way, the development of EH is influenced by the interactions between these four factors. Herein, a 4-dimension- al (4-D) model of EH pathogenesis is de- scribed, including primary approaches and technical considerations. The 4-D model will be useful in understanding the pathogenesis, diagnosis, treatment, and prevention of EH.

In order to explore the potential association between the leptin receptor (LEPR) gene polymorphisms and essential hypertension (EH) risk in the Northern Han Chinese population, we recruited 823 hypertensive subjects and 491 healthy control subjects from the Northern Han Chinese. Genotyping was performed to identify the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms of the LEPR gene. Significant associations were found in a dominant genetic model ([GG+AG] vs. AA), P=0.007, odds ratio (OR)=3.697, 95% confidence interval (CI) 1.442-9.482), and in homozygote comparison (GG vs. AA, P=0.005, OR=3.890, 95% CI 1.501-10.077) for the Gln223Arg polymorphism. No significant association could be found between Lys109Arg or Lys656Asn polymorphism and EH risk. Linkage disequilibrium was detected between the Lys109Arg and Gln223Arg polymorphisms, and haplotype analyses identified that the G-A haplotype was a protective haplotype for EH. Our studies demonstrated that the LEPR Gln223Arg polymorphism had an important role in a patient's susceptibility to EH in the Northern Han Chinese population.

Purpose Mitofusin2 gene (Mfn2, also named Hyperplasia suppressive gene, HSG) is very important in the origin and development of hypertension. However, the mechanism of Mfn2/HSG expression regulation was not uncovered. This study was designed to explore the association of a novel 5'-uncoding region (UCR) -1248 A>G variation of HSG/Mfn2 gene and hypertension. Materials and Methods 472 healthy, normotensive subjects [normotension (NT) group], 454 prehypertensive subjects [prehypertension (PH) group] and 978 hypertensive patients [essential hypertension (EH) group] were screened for an association study between 5'-UCR -1248 A>G of Mfn2/HSG and hypertension by polymerase chain reaction and DNA sequencing after venous blood was drawn and DNA was extracted. Results When comparing the A and G frequency in EH, PH and NT groups, in total, NT group significantly had higher A frequency than in PH group [odds ratio (OR)=1.605, confidence interval (CI) 95%=1.063-2.242, p=0.025] and EH group (OR=5.395, CI 95%=3.783-7.695, pG variation was significantly related with blood pressure level (B=-1.271, Wald=40.914, CI 95%=-1.660 - -0.881, pG variation of Mfn2/HSG gene was a novel variation and may be associated with hypertension in Chinese.

No consensus has been reached on the association between the angiotensinogen gene polymorphism T174M and hypertension risk in the Chinese population. We conducted a meta-analysis to systematically pursue their possible association. Case-control studies in the Chinese and English publications were identified by searching the MEDLINE, EMBASE, CBM, CNKI, Wanfang and VIP databases. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. After this, we selected 16 studies that met the inclusion criteria. In total, the selected studies contributed a study population containing 3828 hypertensive patients and 3251 normotensive controls. We found no statistical association between the T174M polymorphism and hypertension risk in all subjects, in a Han Chinese subgroup or in non-Han Chinese minorities. However, a statistically significant association was observed between the T174M polymorphism and a hypertensive group (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥95 mm Hg) in the dominant genetic model (MM+MT vs. TT: P=0.03, odds ratio=1.71, 95% confidence interval 1.07-2.74, P(heterogeneity)=0.27, I(2)=24%, fixed-effects model). No evidence of publication bias was observed. More studies, especially studies stratified for different stages of hypertension, should be performed in the future to fully examine this question. Studies investigating gene-gene interactions, gene-environment interactions, as well as their mutual interactions will also be important.

No clear consensus has been reached on the α-adducin polymorphism (Gly460Trp) and essential hypertension (EH) risk in Chinese. We conducted a meta-analysis in an effort to systematically explore the possible association. Case-control studies in Chinese and English performed with human subjects were identified by searching the MEDLINE, EMBASE, China Biological Medicine Database, China National Knowledge Infrastructure platform, Wanfang and VIP databases. The fixed-effects model and the random-effects model for dichotomous outcomes were applied to combine the results of the individual studies. We selected 20 studies that met the inclusion criteria, including a total of 5562 patients with hypertension and 4289 controls. Overall, our findings supported the hypothesis that the ADD1 Gly460Trp polymorphism is associated with EH in the Chinese population. A borderline association was found between the tryptophan (Trp) allele of the Gly460Trp variant and hypertension (P=0.05, Odds ratio (OR)=1.08, 95% confidence interval (CI)=1.00-1.17 and P(heterogeneity)=0.02). Significantly increased risk was observed in the recessive genetic model (P=0.0009, OR=1.24, 95% CI=1.09-1.41 and P(heterogeneity)=0.04) as well as in the homozygote comparison (P=0.006, OR=1.25, 95% CI=1.07-1.46 and P(heterogeneity)=0.03). Furthermore, in the subgroup analysis, our results support a positive association among Chinese Han individuals (P=0.001, OR=1.25, 95% CI=1.09-1.42, P(heterogeneity)=0.08, recessive genetic model; P=0.009, OR=1.26, 95% CI=1.06-1.50, P(heterogeneity)=0.03, homozygote comparison). No apparent association was identified in Kazakhs. Our meta-analysis suggests that the Gly460Trp polymorphism might increase the risk of hypertension in Chinese populations, especially in Han Chinese. Further studies investigating gene-gene, gene-environment and mutual interactions are needed to better understand the role of ADD1 in hypertension.

Aim: Hyperplasia suppressor gene/mitofusion-2 (HSG/Mfn2) is a hyperplasia suppressor gene and an essential component of mitochondrial fusion machinery; however, the association between the single nucleotide polymorphism (SNP) of HSG/Mfn2 and hypertension is unclear.Methods: In this study, 542 normotensive subjects (NT group) and 539 hypertensive patients (EH group) were screened for an association study between HSG/Mfn2 and hypertension.Results: The results showed that the genotype distribution and allelic frequency of rs873457, rs2336384, rs1474868, rs4846085 and rs2236055 were significantly different (p lt; 0.05 for all) between EH and NT groups, although those of rs4240897 and rs873458 were not. When comparing the dominant model, significant differences still existed (p lt; 0.05 for all). The allelic frequency of rs4240897 was also slightly different between EH and NT groups (P=0.047). When subgrouped by sex, the genotype distribution and allelic frequency of all the SNPs (except rs873458) were significantly different in male (p lt; 0.05 for all) but not in female groups. For all the SNPs, only the allelic frequency of rs4240897 was obviously different in female NT and EH groups (p lt; 0.01). Logistic regression showed that body mass index and rs873457 were closely associated with BP after adjusting for age. The frequency of the C-G-A-A-A-C-C haplotype was significantly higher in essential hypertensive patients versus control individuals, both in the entire population, in male or female groups (p lt; 0.01 for all). As for other haplotypes, most were only significantly different in the entire population and male subjects.Conclusion: The genetic variations of HSG/Mfn2 may be associated with hypertension in male Chinese.

Background No clear consensus has been reached on the alpha-adducin polymorphism (Gly460Trp) and essential hypertension risk. We performed a meta-analysis in an effort to systematically summarize the possible association. Methodology/Principal Findings Studies were identified by searching MEDLINE and EMBASE databases complemented with perusal of bibliographies of retrieved articles and correspondence with original authors. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. We selected 22 studies that met the inclusion criteria including a total of 14303 hypertensive patients and 15961 normotensive controls. Overall, the 460Trp allele showed no statistically significant association with hypertension risk compared to Gly460 allele (P = 0.69, OR = 1.02, 95% CI 0.94–1.10, Pheterogeneity

Background Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension. Methods Hypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study. Results Hypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C). Conclusion C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.

A pilot study was conducted to investigate blood pressure level and vasoactive factors (VFs) among age- and sex-matched normotensive (NT), prehypertensive (PH), and hypertensive (EH) subjects. The results showed that angiotensin, arginine vasopressin, and endothelin were significantly higher, while adrenomedullin and calcitonin gene-related peptide were lower in the EH group than in the PH and NT groups. Nitric oxide synthase was not different among the three groups. There was a dose-response relationship between VFs and BP status. The results suggested that changes in blood VFs might be early warning signs of the development of prehypertension to hypertension, and important biomarkers for the early prevention of prehypertension.