Risk Factor For Essential Hypertension Research Articles

CACNA1C rs1006737 SNP increases the risk of essential hypertension in both Chinese Han and ethnic Russian people of Northeast Asia.

Voltage-gated Ca2+ channels play a key role in the regulation of arterial tone and blood pressure. The aim of this study was to determine whether the association of calcium voltage-gated channel subunit alpha1 C (CACNA1C) rs1006737 with essential hypertension (EH) exists in both Chinese Han and ethnic Russian populations of Northeast Asia. We used a case-control study of 2 ethnic groups in the same latitude geographical area to investigate the association between the susceptibility of EH and rs1006737 polymorphism. A total of 1512 EH patients and 1690 controls in Chinese Han people (Heilongjiang Provence, China), 250 EH patients, and 250 controls in ethnic Russian people (Chita, Russia), participated in this study. All participants were genotyped using the TaqMan SNP genotyping assay (Agena Company). Baseline characteristics and the minor allele frequencies of rs1006737 vary substantially among common Chinese Han and ethnic Russian people. Allele A was found to be a risk factor for EH in Chinese Han [(odds ratio) OR 1.705, (confidence interval) 95% CI: 1.332–2.182, P < .001] and ethnic Russian (OR 1.437; 95% CI: 1.110–1.860, P = .006). The GA genotype was significantly associated with an increased risk of hypertension (OR 1.538, 95% CI: 1.188–1.991, P = .001) for Chinese Han people, and the AA genotype (OR 2.412, 95% CI: 1.348–4.318, P = .003) for ethnic Russian people. The results of this study indicate that the A allele of the variant rs1006737 in the CACNA1C gene may be a useful genetic marker for EH risk prediction in Chinese Han and ethnic Russian populations.

Exploration of the risk factors of essential hypertension with hyperhomocysteinemia: A hospital-based study and nomogram analysis

OBJECTIVES:To explore the risk factors of essential hypertension with hyperhomocysteinemia (H-type hypertension) and design a nomogram to predict this risk.METHODS:A hospital-based study was conducted on 1,712 individuals, including 282 patients with H-type hypertension, 105 patients with simple hypertension, 645 individuals with hyperhomocysteinemia, and 680 healthy controls. Logistic regression and nomogram models were applied to evaluate the risk factors.RESULTS:Logistic regression showed that advanced age, male sex, high body mass index (BMI), high total cholesterol levels, high glucose levels, and high creatinine levels were risk factors of H-type hypertension in the healthy population and were integrated into the nomogram model. Advanced age, male sex, high BMI, high total cholesterol levels, and high glucose levels were shown to be risk factors of H-type hypertension in the hyperhomocysteinemia population. Male sex and high creatinine levels were shown to be risk factors of H-type hypertension in the hypertension population. Nomogram analysis showed that the total factor score ranged from 106 to 206, and the corresponding risk rate ranged from 0.05 to 0.95.CONCLUSIONS:Men are more likely to have H-type hypertension, and advanced age, high BMI, high total cholesterol levels, and high glucose levels are risk factors of H-type hypertension in healthy and hyperhomocysteinemia populations. Furthermore, high creatinine level is a risk factor of H-type hypertension in healthy and hypertension populations. Nomogram models may be used to intuitively evaluate H-type hypertension risk and provide a basis for personalized interventions.

Hsa_circ_0037897 may be a risk factor for essential hypertension via hsa-miR-145-5p

ABSTRACT Objectives: This study aims to investigate the association between hsa_circ_0037897 and essential hypertension (EH) and to evaluate the diagnostic value of biomarker hsa_circ_0037897 in EH. Methods: This study included 92 EH patients and 92 sex- and age- (±3 years) matched subjects as control. qRT-PCR was performed to measure the expression level of circRNA and miRNA. Logistic regression analysis model was used to assess independent association between hsa_circ_0037897 and EH. Results: The expression level of hsa_circ_0037897 in EH patients was significantly higher (p < .001) compared to the control group, while hsa-miR-145-5p had significantly lower expression(p = .002) than the control group. The area under the ROC curve (AUC) of hsa_circ_0037897 was 0.656. Furthermore, the AUC increased to 0.714 when hsa_circ_0037897 was combined with hsa-miR-145-5p, BMI and smoking. Conclusion: The present results suggested that the high expression of hsa_circ_0037897 may be a risk factor for EH, and hsa_circ_0037897 has certain diagnostic value for EH.

ThemicroarrayidentificationcircularRNA hsa_circ_0105015up-regulated involvinginflammationpathwayin essential hypertension.

BackgroundEssential hypertension (EH) is an inflammatory disease, and endothelial dysfunction induced by chronic inflammation is one of the pathogeneses of EH. The expression of some inflammatory mediators may be regulated by the interaction of circular RNAs (circRNAs) and microRNAs (miRNAs).MethodsAn Agilent human circRNA microarray was used to identify the expression profile of circRNAs in EH. qRT‐PCR was used to evaluate the relative expression of circRNAs in 48 pairs of human whole blood samples (sex and age ± 3 years matched) and endothelial cells. TNF‐α was applied to induce endothelial cells inflammation. CircRNA‐miRNA network was predicted by MiRanda software.ResultsThere were 287 circRNAs differentially expressed in the microarray. The top 10 up‐regulated circRNAs in the EH group were hsa_circ_0014243, hsa_circ_0133228, hsa‐circRNA14116‐3, hsa_circ_0079536, hsa‐circRNA13649‐1, hsa_circ_0117886, hsa_circ_0007075, hsa‐circRNA15285‐1, hsa‐circRNA10088‐9, and hsa‐circRNA14119‐10; the top 10 down‐regulated circRNAs were hsa_circ_0100094, hsa_circ_0127342, hsa_circ_0093773, hsa_circ_0096334, hsa_circ_0131618, hsa_circ_0063886, hsa_circ_0097804, hsa_circ_0126640, hsa‐circRNA8935‐1, and hsa_circ_0039978 (fold change in descending order). Hsa_circ_0105015 has two predicted binding sites with hsa‐miR‐637. The relative expression of hsa_circ_0105015 in EH patients was significantly higher than healthy controls (P = .002), and similar results appeared in TNF‐α‐induced endothelial cells. The area under the curve after hsa_circ_0105015 combined with hsa‐miR‐637 was 0.703, P < .001.ConclusionHyperexpression of hsa_circ_0105015 is a significant risk factor of EH and its association with EH involves inflammatory pathways. Hyperexpression of hsa_circ_0105015 combined with hypoexpression of hsa‐miR‐637 indicates vascular inflammation or endothelial dysfunction and has potential as a biomarker for early diagnosis of EH.

A study to evaluate risk factors and factors associated with non-adherence to the prescribed treatment among essential hypertensive patients attending tertiary care hospital

Background: Prevalence of hypertension is on rising trend with rise in life style and behavioral changes. It is also a major risk factor for most of the dreadful conditions like coronary artery disease, stroke, etc. Medication adherence would help in reducing the chance of occurrence of such complications. Thus objectives of study are 1) to evaluate the risk factors of hypertension among the diagnosed essential hypertensive patients; and 2) to assess the magnitude and the factors associated with non-adherence to the prescribed treatment.Methods: A hospital based cross-sectional study among 71 participants was conducted, using a pre-structured questionnaire and physical examination to assess risk factors of hypertension and CULIG’s 16 questionnaire medication adherence scale to assess the non-adherence. Data analysed with proportions and Chi square test.Results: Out of 71 participants, 60 (84.5%) were found to be non-adherent to their anti-hypertensive medication and factors like being male (p=0.0055), alcohol consumption (p=0.0485) and paid medication (p=0.0091) were found to be significantly affecting the medication non-adherence. Positive family history, sedentary life style, preference of extra salt and smoking/tobacco products usage were the most common risk factors of essential hypertension observed along with others.Conclusions: The participants who experienced the complications/ill effects of hypertension were more adherent as compared to others. Factors which are responsible for non -adherence need to be addressed and appropriate interventions required to improve adherence by educating the people about its importance in prevention of complications.

Serum uric acid level in Bangladeshi adults with essential hypertension

Background: The association of hyperuricemia with various cardiovascular risk factors has often led to the debate of whether hyperuricemia is an independent risk factor for essential hypertension (HTN). The current study was conducted to see the relationship between serum uric acid and essential HTN in Bangladeshi adults.Methods: In this cross-sectional study, conducted in a tertiary hospital of Bangladesh, 155 patients with essential hypertension (newly detected or on treatment) aged ≥18 years and 100 age-sex matched normotensive subjects were investigated. Serum uric acid, plasma glucose, serum creatinine, and lipid profile were measured in all in fasting samples.Results: The frequency of hyperuricemia was higher in the hypertensive group in comparison to the normotensive control group (29.7% vs. 6.0%, p&lt;0.001). Serum uric acid level was higher in the hypertensive subjects than the controls (6.10±0.88 vs. 5.38±0.54 mg/dL, mean±SD, p&lt;0.001). In the hypertensive group, subjects with stage II HTN had higher serum uric acid than those with stage I HTN (6.46±0.83 vs. 5.72±0.78 mg/dL, mean±SD, p&lt;0.001). In the hypertensive group, uric acid level showed significant positive correlations with both systolic and diastolic blood pressure though in the control group uric acid showed such correlation with systolic BP only.Conclusion: Patients with essential hypertension had higher serum uric acid compared to normotensive controls; uric acid level showed positive correlations with systolic and diastolic BP in the hypertensive subjects.

Association of the interaction between the rs9619311 and rs402007 polymorphisms and smoking with essential hypertension in Chinese Han population.

Background:To assess the association of the interaction between the rs9619311 and rs402007 polymorphisms and smoking with essential hypertension (EH) in a Chinese Han population.Method:Peripheral blood samples were extracted from 422 EH patients and 280 normotensive (NT) patients in a Chinese Han population. A whole blood genomic DNA extraction kit was used to extract genomic DNA from the blood samples. Polymerase chain reaction restriction fragment length polymorphism was used to detect the rs402007 polymorphism of a disintegrin and metalloproteinase with thrombospondin type motifs 1 gene and the rs9619311 polymorphism of the tissue inhibitor of metalloproteinase-3 gene. The distributions of the genotypes and alleles between the 2 study groups (EH and NT) were compared. The main risk factors for EH were determined by using logistic regression analysis. The effects of gene-gene and gene-smoking interactions on EH were analyzed using multifactor dimensional reduction.Results:The frequencies of the rs402007 GC + CC genotype and the C allele were significantly different between the EH and NT groups (0.68 vs 0.57, χ2 = 8.99a, P = .003, odds ratio [OR] = 1.19; 0.45 vs 0.32, χ2 = 22.16a, P < .001, OR = 1.38). The frequencies of the rs9619311 TC + CC genotype and the C allele were also significantly different between the 2 groups (0.33 vs 0.25, χ2 = 4.51a, P = .04, OR = 1.44; 0.18 vs 0.13, χ2 = 7.03a, P = .01, OR = 1.50). Logistic regression analysis suggests that the rs402007 and rs9619311 polymorphisms are independent risk factors for EH (OR = 2.37, 1.86; P < .001, respectively). The multifactor dimensionality redundant analysis results showed that the interaction among rs402007, rs9619311, and smoking was statistically significant (P = .001).Conclusions:A disintegrin and metalloproteinase with thrombospondin type motifs 1 rs402007 and tissue inhibitor of metalloproteinase-3 rs9619311 polymorphisms are associated with EH in a Chinese Han population, and there was a positive interaction among rs402007, rs9619311, and smoking.

The up-regulated hsa-circRNA9102-5 may be a risk factor for essential hypertension.

BackgroundThe present study was aimed to investigate the expression levels of circular RNAs (circRNAs) in the peripheral blood of essential hypertension (EH) patients and healthy controls (HC). On this basis, we tried to explain the possible role of circRNAs in the progression of EH and their potential as diagnostic biomarkers of EH.MethodsFirst, we analyzed the differentially expressed circRNAs in peripheral blood obtained from the finished microarray analysis and selected four circRNAs under strict standards. Then, quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to measure the expression levels of the selected circRNAs in a total of 192 blood samples, consisting of 96 HC and 96 diagnosed EH patients. Bioinformatics prediction of the target microRNAs (miRNAs) was performed for differentially expressed circRNAs, and the circulating vascular‐related miRNAs were selected for qRT‐PCR analysis to determine their expression levels.ResultsHsa‐circRNA9102‐5 (11.7 ± 1.06 vs 12.13 ± 1.11, P = .007) was up‐regulated in the patients group which was diagnosed with EH, as compared to the HC group, and was involved in the regulation of EH by sponging hsa‐miR‐150‐5p. The area under the ROC curve (AUC) of the model was 0.620, using hsa‐circRNA9102‐5 as an independent predictor. Furthermore, the AUC was increased to 0.728 when hsa‐circRNA9102‐5 was combined with hsa‐miR‐150‐5p and multiple other factors, as a combined predictor.ConclusionsThe present results suggested that hsa‐circRNA9102‐5 may have played a crucial role in the development of EH by sponging hsa‐miR‐150‐5p, which showed great potential as a novel target.

Glutathione S-transferase M1 and T1 genes deletion polymorphisms and risk of developing essential hypertension: a case-control study in Burkina Faso population (West Africa)

BackgroundGlutathione S-transferases play a key role in the detoxification of persistent oxidative stress products which are one of several risks factors that may be associated with many types of disease processes such as cancer, diabetes, and hypertension. In the present study, we characterize the null genotypes of GSTM1 and GSTT1 in order to investigate the association between them and the risk of developing essential hypertension.MethodsWe conducted a case-control study in Burkina Faso, including 245 subjects with essential hypertension as case and 269 control subjects with normal blood pressure. Presence of the GSTT1 and GSTM1 was determined using conventional multiplex polymerase chain reaction followed by gel electrophoresis analysis. Biochemical parameters were measured using chemistry analyzer CYANExpert 130.ResultsChi-squared test shows that GSTT1-null (OR = 1.82; p = 0.001) and GSTM1-active/GSTT1-null genotypes (OR = 2.33; p < 0.001) were significantly higher in cases than controls; the differences were not significant for GSTM1-null, GSTM1-null/GSTT1-active and GSTM1-null/GSTT1-null (p > 0.05). Multinomial logistic regression revealed that age ≥ 50 years, central obesity, family history of hypertension, obesity, alcohol intake and GSTT1 deletion were in decreasing order independent risk factors for essential hypertension. Analysis by gender, BMI and alcohol showed that association of GSTT1-null with risk of essential hypertension seems to be significant when BMI < 30 Kg/m2, in non-smokers and in alcohol users (all OR ≥ 1.77; p ≤ 0.008). Concerning GSTT1, GSTM1 and cardiovascular risk markers levels in hypertensive group, we found that subjects with GSTT1-null genotype had higher waist circumference and higher HDL cholesterol level than those with GSTT1-active (all p < 0.005), subjects with GSTM1-null genotype had lower triglyceride than those with GSTM1-active (p = 0.02) and subjects with the double deletion GSTM1-null/GSTT1-null had higher body mass index, higher waist circumference and higher HDL cholesterol than those with GSTM1-active/GSTT1-active genotype (all p = 0.01).ConclusionOur results confirm that GSTT1-null genotype is significantly associated with risk of developing essential hypertension in Burkinabe, especially when BMI < 30 Kg/m2, in non-smokers and in alcohol users, and it showed that the double deletion GSTM1-null/GSTT1-null genotypes may influence body lipids repartition.

Microarray Profiling of Circular RNA Identifies hsa_circ_0126991 as a Potential Risk Factor for Essential Hypertension

Essential hypertension (EH), a major cause of cardiovascular diseases, is an important public health issue. However, the molecular mechanisms involved in EH remain unknown. Circular RNA (circRNA) is a novel promising biomarker for the disease. The purpose of the present study was to determine the expression of circRNAs in the blood of EH patients and to evaluate the performance of circRNA for early diagnosis of EH. A total of 178 subjects were recruited in the case-control study. Initial screening was done by using the Agilent human circRNA microarray followed by qRT-PCR validation. Finally, miRNAs were combined with circRNAs to create a new early prediction model for EH. The expression level of hsa_circ_0126991 in EH patients was significantly higher in comparison with healthy controls (p < 0.0001). Using the interaction of miR-10a-5p in combination with hsa_circ_0126991 led to a sensitivity of 0.708, a specificity of 0.764, and combined area under the curve of 0.774 (95% CI: 0.705-0.843) for early diagnosis of EH. In summary, the present study uncovered a novel perspective that hyperexpression of hsa_circ_0126991 is correlated with the risk of EH and may serve as a stable biomarker for early diagnosis of EH.

Traditional risk factors for essential hypertension: analysis of their specific combinations in the EPIC-Potsdam cohort

Appropriate interventions might improve the prevention of essential hypertension. This requires a comprehensive view of modifiable lifestyle factors (MLFs) distribution and effect. To determine how six MLFs (general adiposity, abdominal adiposity, alcohol consumption, smoking, diet, physical inactivity) for risk of hypertension are distributed and how their combinations affect the risk, a prospective study cohort of 11,923 healthy participants from the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study was used. Of these, 1,635 developed hypertension during a mean follow-up of 10.3 years. Mutually exclusive combinations, clustering and interactions of MLFs were then investigated stratifying by sex, Hazard Ratios (HRs) and Population Attributable Risks (PARs%) were calculated. General adiposity alone was sufficient to increase the risk of hypertension (HR = 1.86, PAR% 3.36), and in this cohort it played a major role in enhancing the risk of hypertension, together with smoking and physical inactivity. MLFs had a different impact and a different modulation of risk in women and men, and they showed a remarkable tendency to occur in specific patterns with higher prevalence than expected. This indication can help to promote a holistic approach through multifactorial preventive strategies addressing more than a factor at a time. For prevention of hypertension addressing adiposity together with smoking, promoting at the same time physical activity should be the first choice.

A potential risk factor of essential hypertension in case-control study: MicroRNAs miR-10a-5p

ABSTRACTBackground: Essential hypertension is a multifactorial disease with high morbidity. The researches on the influence of genes on the disease are still in its infancy, and the mechanism of gene regulation is not clear. MiRNAs are key molecules that regulate the expression control of protein-coding or protein-non-coding RNA. It may be an important biological molecule risk factor for essential hypertension.Methods: A case-control study with 98 EH and 98 non-EH was conducted in our experiment. The candidate miRNAs including miR-10a-5p and miR-497-5p were detected and verified by qRT-PCR.Results: The expression level of miRNA in EH cases was significantly lower than the healthy control (P = 0.005). In addition, the relative expression of miR-10a-5p was closely positive correlated with DBP (r = 0.162, P = 0.023) and SBP (r = 0.223, P = 0.002). After adjusting confound factors, the result of the logistic regression indicated that hypo-expression of miR-10a-5p is a risk factor for EH (OR(95%CI) = 1.676(1.302,2.157), adjusted P < 0.0001). And the ROC analysis shows that the combined line with BMI and miR-10a-5p was a values marker for EH (AUC: 0.728, P < 0.0001).Conclusions: Lower expression of miR-10a-5p, as the key role, is significantly related to the risk of EH and maybe as a potential biomolecule for EH.

Association of the gene polymorphisms of BMPR2, ACVRL1, SMAD9 and their interactions with the risk of essential hypertension in the Chinese Han population.

Objective: Genetic factors are involved in the occurrence, development, and progression of essential hypertension (EH). To study the association between single nucleotide polymorphisms (SNPs) of the rs6435156 and rs1048829 loci of the bone morphogenetic protein receptor type 2 (BMPR2) gene, the rs121909287 and rs121909284 loci of the activin receptor-like kinase 1 (ACVRL1) gene, and the rs397514716 and rs121918359 loci of the mothers against decapentaplegic homolog 9 (SMAD9) gene with the risk of EH in the Chinese Han population. Materials and methods: A total of 460 EH patients and 460 healthy controls were recruited for the study. Genomic DNA of white blood cells was extracted, and the genotypes were analyzed by Sanger sequencing after polymerase chain reaction amplification. Multi-factor dimensionality reduction (MDR) was used to analyze the effect of gene–environment interactions on EH risk. Results: The risk of EH increased in the BMPR2 gene rs6435156 locus dominant model (adjusted odds ratio [OR] = 1.572, 95% confidence interval [CI]: 1.385–1.765, P<0.001) and recessive model (adjusted OR = 1.926, 95% CI: 1.693–2.067, P<0.001). The risk of EH increased in the rs1048829 recessive model (adjusted OR = 1.444, 95% CI: 1.142–1.696, P=0.003). The risk of EH increased in the recessive model of the ACVRL1 gene rs121909287 locus (adjusted OR = 1.403, 95% CI: 1.101–1.660, P=0.008). The risk of EH increased in the SMAD9 gene rs397514716 locus dominant model (adjusted OR = 1.370, 95% CI: 1.183–1.559, P<0.001) and recessive model (adjusted OR = 1.803, 95% CI: 1.470–1.983, P<0.001). The CG haplotype of the rs6435156 and rs1048829 loci of the BMPR2 gene, the CC haplotype of the ACVRL1 gene rs121909287 and rs121909284 loci, and the CC haplotype of the rs397514716 and rs121918359 loci of the SMAD9 gene were factors that protect against EH, whereas the TT haplotype of the rs6435156 and rs1048829 loci in the BMPR2 gene was a risk factor for EH. MDR analysis showed that the BMPR2 gene rs6435156 locus TT genotype carriers, the SMAD9 gene rs397514716 locus TT genotype carriers, and alcohol drinkers had the highest EH risk (OR = 4.523, 95% CI: 2.235–6.871, P<0.001). Conclusion: The SNPs of the rs6435156 and rs1048829 locus in the BMPR2 gene, the rs121909287 loci in the ACVRL1 gene, and the rs397514716 locus in the SMAD9 gene were associated with a risk of EH in Han Chinese.

A Prediction Model of Essential Hypertension Based on Genetic and Environmental Risk Factors in Northern Han Chinese.

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.

Association of ACE2 genetic polymorphisms withhypertension-related target organ damages in south Xinjiang

Essential hypertension (EH) is a principal contributing factor inworldwide cardiovascular disease mortality. Although interventions that minimizeenvironmental risk factors for EH are associated with reduced cardiovasculardisease, such approaches are limited for individuals with high genetic EH risk. Inthis study, we investigated possible associations between ACE2 polymorphisms andhypertension-related target organ damages in south Xinjiang, China. Four hundred andtwo hypertensive patients were enrolled as study participants in an EH group, and233 normotensive individuals were enrolled as control subjects. Participants wererecruited from the south Xinjiang region. Fourteen ACE2 polymorphisms were genotypedby matrix-assisted laser desorption ionization time-of-flight mass spectrometry.Risk genotypes of rs2074192 (TT+CT, OR = 1.72, 95% CI: 1.17–2.53), rs2106809 (TT,OR = 1.71, 95% CI: 1.13–2.58), rs4240157 (CC+CT, OR = 1.99, 95% CI: 1.17–3.41),rs4646155 (TT+CT, OR = 1.94, 95% CI: 1.06–3.54), rs4646188 (TT+CT, OR = 3.25, 95%CI: 1.95–5.41), rs4830542 (CC+CT, OR = 1.88, 95% CI: 1.10–3.23), and rs879922(CC+CG, OR = 4.86, 95% CI: 2.74–8.64) were associated with EH. Hypertensive patientscarrying the control genotype of rs2074192 (CC, OR = 2.37, 95% CI: 1.28–4.39) wereassociated with CAS ≥50%, while those carrying a high-EH-risk genotype of rs4240157(OR = 2.62, 95% CI: 1.24–5.54), rs4646155 (OR = 2.44, 95% CI: 1.16–5.10), orrs4830542 (CC+CT, OR = 2.20, 95% CI: 1.03–4.69) were associated with atrialfibrillation (AF), larger left atrial diameter, and higher levels ofrenin–angiotensin–aldosterone system (RAAS) activation (renin and angiotensin I/II).In conclusion, the ACE2 variant rs2074192 was associated with EH and EH with CAS≥50%, while 3 ACE2 variants (rs4240157, rs4646155, and rs4830542) were associatedwith EH- and hypertension-related AF and left atrial remodeling in south Xinjiang,China.

Relationship between the NF-κB1-94ins/del ATTG locus polymorphism and risk of hypertension in the Chinese Han population

ABSTRACTObjective: The onset of essential hypertension is the result of a combination of genetic factors and the environment. The nuclear factor (NF)-κB1-94ins/del ATTG locus polymorphism is associated with the occurrence of various diseases. The purpose of this study was to find out the relationship between the NF-κB1-94ins/del ATTG locus polymorphism and the risk of hypertension in the Chinese Han population.Methods: A total of 585 Chinese Han patients with essential hypertension and 585 Chinese Han healthy volunteers were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to analyze the genotype of the NF-κB1-94ins/del ATTG locus in all the subjects.Results: For the NF-κB1-94ins/del ATTG locus, the dominant (adjusted odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.13–1.54, P < 0.001), recessive (adjusted OR = 1.17, 95% CI = 1.02–1.32, P = 0.03) and additive (adjusted OR = 1.19, 95% CI = 1.03–1.36, P = 0.01) models showed significant increase in the risk of hypertension. The NF-κB1-94ins/del ATTG locus II genotype was an independent risk factor for hypertension (OR = 1.15, 95% CI = 0.78–1.69, P = 0.02). The interaction between the NF-κB1-94ins/del ATTG locus polymorphism and BMI, alcohol consumption, and diabetes significantly increased the risk of hypertension (OR = 1.71, 95% CI = 1.26–1.86, P < 0.01).Conclusion: The NF-κB1-94ins/del ATTG polymorphism is an independent risk factor for essential hypertension. The NF-κB1-94ins/del ATTG locus, obesity, drinking, and diabetes also interact to yield a higher risk of hypertension.

Association of single nucleotide polymorphisms of LEPR gene with essential hypertension among ethnic Mongolian and Han Chinese from Inner Mongolia region

To assess the association of single nucleotide polymorphisms (SNPs) of leptin receptor (LEPR) gene with essential hypertension (EH) and body mass index (BMI) among ethnic Mongolian and Han Chinese from Inner Mongolia region. In total 411 Han Chinese patients with EH and 480 healthy controls, together with 658 Mongolian patients with EH and 403 healthy controls, were collected. The SNPs of the LEPR gene were determined with ligase detection reaction (LDR). Logistic regression was used to analyze the association of the polymorphisms of each locus with EH and BMI. MDR software was used to analyze the interaction between above loci and environmental factors. Genotypic frequencies of LEPR gene rs7555955, rs1137100 and rs1137101 loci had differed significantly among ethnic Hans with EH and the control group (All P<0.05). While those of rs7555955, rs1805094, rs1137100, rs11579567, rs1805134 and rs6669354 loci had differed significantly among ethnic Mongolians with EH and the control group (All P<0.05). After adjustment for confounders, logistic regression analysis indicated that age (OR=2.97, 95%CI:1.94-3.99), BMI (OR=3.93, 95%CI:2.91-5.96), and rs1137101 (AA) (OR=3.96, 95%CI:1.32-11.90) were independent risk factors for EH among ethnic Hans, while age (OR=2.99, 95%CI:2.98-4.57), BMI (OR=3.03, 95%CI:1.05-1.27), rs7555955 (AG, AA) (OR=12.12, 95%CI:2.80-52.43; OR=6.35, 95%CI:1.44-27.94), and rs7555955 (GG) were independent risk factors for EH among ethnic Mongolians (P<0.05). Age and BMI are independent risk factors for EH in both ethnic Han and Mongolian Chinese. rs1137101 locus is associated with EH among ethnic Hans, while rs7555955 locus is associated with EH among ethnic Mongolians.

Association of mitofusin 2 methylation and essential hypertension: a case-control study in a Chinese population.

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.

A potential risk factor of essential hypertension in case-control study: Circular RNA hsa_circ_0037911

BackgroundEssential hypertension (EH) is a high prevalence with multifactorial diseases. Human studies on the impact of genes on this disease are just in the initial stage, the mechanism of gene regulation is still remains unclear. Circular RNAs (circRNAs) as a continuous cycle of covalent closure, RNA molecules added to the 3′-5′ end covalently bound by the formation of incidental event. CircRNAs may be an important biomolecule in revealing the molecule regulate mechanisms of EH. MethodsThe circRNAs were selected and validated with qRT-PCR followed. Our experiment was conducted with case-control studies among 200 EH participants. The t-test was used to evaluate the different expression of circRNAs and miRNAs, the significance of which was set as p < 0.05. ResultsThe hsa_circ_0037911 expression level in EH cases were significantly higher than healthy controls (p = 0.005). There was still important significance when adjusted by logistic regression (adjusted p = 0.026). We also found that hsa_circ_0037911 was an effective marker of EH (area under curve = 0.627; p = 0.002). The levels of hsa_circ_0037911 were significantly differences in gender, BMI, smoking and drinking among EH cases. There was a positive correlation between Serum creatinine (Scr) and hsa_circ_0037911. ConclusionsOur findings suggested that higher expression hsa_circ_0037911 may be key circRNAs for EH development by changing the concentration of Scr and could be a stable biomarker for early diagnosis of EH.

Polymorphism of the DNA methyltransferase 1 gene is associated with the susceptibility to essential hypertension in male

ABSTRACTEssential hypertension is a leading global public health issue, billions of people suffered from it every year. Recently, multiple evidence suggests that DNA methylation play an important role in regulating blood pressure. Here, we tested the risk for essential hypertension conferred by single nucleotide polymorphisms (SNPs) within DNA methyltransferase 1 (DNMT1). Three loci (rs2228611, rs2228612, and rs16999593) were selected to be analyzed in 3410 cases and 1307 normal controls in southern Chinese aged 60 or above. No significant association with essential hypertension was observed for rs2228612 and rs16999593. A higher risk of essential hypertension was found in the minor A allele of rs2228611 in the codominant and recessive model (P < 0.05). After stratified by sex, this association was found in male but not female. Furthermore, this difference was abolished after BMI adjustment in the whole population and reduced in male. In addition, the mutation rate of rs2228611 was higher in the obesity group compared with the normal weight group of male. Intriguingly, rs2228611 was also a risk factor of essential hypertension in normal weight male. These findings indicated that rs2228611 might contribute to male hypertension via BMI-dependent mechanisms in obesity male and BMI-independent mechanisms in normal weight male.