Risk Of Essential Hypertension Research Articles

Interplay Between Plasma Glycine and Branched-Chain Amino Acids Contributes to the Development of Hypertension and Coronary Heart Disease.

Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease. The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. P-gain statistic >10 identified instruments associated with tBCAAs/glycine ratio significantly stronger compared with individual amino acids. Outcomes of genome-wide association study on hypertension and CHD were derived from the UK Biobank (nonoverlapping sample), FinnGen, and CARDIoGRAMplusC4D. The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.226 [95% CI, 1.160-1.296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio (P-gain >10) was a risk factor for hypertension (meta-analyzed inverse-variance weighted causal estimate 0.45 log odds ratio/SD (95% CI, 0.26-0.64) and CHD (0.48 [95% CI, 0.29-0.67]) with an absolute effect significantly larger compared with the effect of glycine (-0.06 [95% CI, -0.1 to -0.03] and -0.08 [95% CI, -0.11 to -0.05], respectively) or tBCAAs (0.22 [95% CI, 0.09-0.34] and 0.12 [95% CI, 0.01-0.24], respectively). The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs.

Causal Relationship Between Branched-Chain Amino Acids and Hypertension: AMendelian Randomization Study.

This study aimed to investigate the causal relationships between branched-chain amino acids (BCAAs) and the risks of hypertension via meta-analysis and Mendelian randomization analysis. A meta-analysis of 32 845 subjects was conducted to evaluate the relationships between BCAAs and hypertension. In Mendelian randomization analysis, independent single-nucleotide polymorphisms associated with BCAAs at the genome-wide significance level were selected as the instrumental variables. Meanwhile, the summary-level data for essential hypertension and secondary hypertension end points were obtained from the FinnGen study. As suggested by the meta-analysis results, elevated BCAA levels were associated with a higher risk of hypertension (isoleucine: summary odds ratio, 1.26 [95% CI, 1.08-1.47]; leucine: summary odds ratio, 1.28 [95% CI, 1.07-1.52]; valine: summary odds ratio, 1.32 [95% CI, 1.12-1.57]). Moreover, the inverse variance-weighted method demonstrated that an elevated circulating isoleucine level might be the causal risk factor for essential hypertension but not secondary hypertension (essential hypertension: odds ratio, 1.22 [95% CI, 1.12-1.34]; secondary hypertension: odds ratio, 0.96 [95% CI, 0.54-1.68]). The increased levels of 3 BCAAs positively correlated with an increased risk of hypertension. Particularly, elevated isoleucine level is a causal risk factor for essential hypertension. Increased levels of leucine and valine also tend to increase the risk of essential hypertension, but further verification is still warranted.

Causal associations between gastroesophageal reflux disease and essential hypertension: A bidirectional Mendelian randomization study.

Clinical studies have reported that patients with gastroesophageal reflux disease (GERD) have a higher prevalence of hypertension. To performed a bidirectional Mendelian randomization (MR) analysis to investigate the causal link between GERD and essential hypertension. Eligible single nucleotide polymorphisms (SNPs) were selected, and weighted median, inverse variance weighted (IVW) as well as MR egger (MR-Egger) regression were used to examine the potential causal association between GERD and hypertension. The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs. The MR-Egger intercept test, Cochran's Q test and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of single instrumental variable. IVW analysis exhibited an increased risk of hypertension (OR = 1.46, 95%CI: 1.33-1.59, P = 2.14E-16) in GERD patients. And the same result was obtained in replication practice (OR = 1.002, 95%CI: 1.0008-1.003, P = 0.000498). Meanwhile, the IVW analysis showed an increased risk of systolic blood pressure (β = 0.78, 95%CI: 0.11-1.44, P = 0.021) and hypertensive heart disease (OR = 1.68, 95%CI: 1.36-2.08, P = 0.0000016) in GERD patients. Moreover, we found an decreased risk of Barrett's esophagus (OR = 0.91, 95%CI: 0.83-0.99, P = 0.043) in essential hypertension patients. We found that GERD would increase the risk of essential hypertension, which provided a novel prevent and therapeutic perspectives of essential hypertension.

The causal effect of air pollution on the risk of essential hypertension: a Mendelian randomization study.

Air pollution poses a major threat to human health by causing various illnesses, such as cardiovascular diseases. While plenty of research indicates a correlation between air pollution and hypertension, a definitive answer has yet to be found. Our analyses were performed using the Genome-wide association study (GWAS) of exposure to air pollutants from UKB (PM2.5, PM10, NO2, and NOX; n = 423,796 to 456,380), essential hypertension from FinnGen (42,857 cases and 162,837 controls) and from UKB (54,358 cases and 408,652 controls) as a validated cohort. Univariable and multivariable Mendelian randomization (MR) were conducted to investigate the causal relationship between air pollutants and essential hypertension. Body mass index (BMI), alcohol intake frequency, and the number of cigarettes previously smoked daily were included in multivariable MRs (MVMRs) as potential mediators/confounders. Our findings suggested that higher levels of both PM2.5 (OR [95%CI] per 1 SD increase in predicted exposure = 1.24 [1.02-1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02-1.06], p = 7.58E-05 from UKB) and PM10 (OR [95%CI] = 1.24 [1.02-1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02-1.06], p = 7.58E-05 from UKB) were linked to an increased risk for essential hypertension. Even though we used MVMR to adjust for the impacts of smoking and drinking on the relationship between PM2.5 exposure and essential hypertension risks, our findings suggested that although there was a direct positive connection between them, it is not present after adjusting BMI (OR [95%CI] = 1.05 [0.87-1.27], p = 6.17E-01). Based on the study, higher exposure to PM2.5 and PM10 increases the chances of developing essential hypertension, and this influence could occur through mediation by BMI. Exposure to both PM2.5 and PM10 is thought to have a causal relationship with essential hypertension. Those impacted by substantial levels of air pollution require more significant consideration for their cardiovascular health.

Nomogram developed with APOA5 genetic variant rs662799 and clinical characteristics predicting risk of essential hypertension in a Chinese population.

The apolipoprotein A5 (APOA5) gene has been identified as a key regulatory factor in triglyceride (TG) metabolism and plasma lipid levels. Genetic polymorphisms of APOA5 have been linked to an elevated risk of atherosclerosis, metabolic syndrome, stroke, and coronary artery disease. The rs662799 variant is a single nucleotide polymorphism (SNP) that occurs at a specific position within the APOA5 gene. However, the association between rs662799 polymorphism and essential hypertension (EHT) remains unclear. The study aimed to comprehensively examine the potential correlation between the rs662799 polymorphism and the susceptibility to EHT in a Chinese population using a systematic analysis. In a case study conducted at the First Affiliated Hospital of Xinjiang Medical University between Jan 2019 and Dec 2021, we examined a total of 700 cases of EHT along with 700 corresponding controls. The serum concentrations of various lipid parameters were measured by enzymatic method, while the genotyping of the SNP was performed using the improved multiplex ligation detection reaction (iMLDR) method. The independent risk factors of EHT were identified from multivariable logistic regression analysis. The nomogram prediction model that incorporated the APOA5 genetic variations and clinical variables was constructed. In addition, receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test were conducted to determine the performance of the nomogram model. The optimal threshold was calculated based on Youden index. Our study revealed a higher prevalence of the G allele of the rs662799 variant in individuals diagnosed with EHT compared to the control group. Logistic regression analysis indicated that with the adjustment of other confounders, the observed difference between the two groups remained statistically significant [odds ratio (OR) =1.519; 95% confidence interval (CI): 1.203-1.917; P<0.001]. Based on 8 independent risk factors including APOA5 rs662799 G allele, age, body mass index (BMI), smoking, diabetes, education, low-density lipoprotein cholesterol (LDL-C), and TG, we constructed a novel risk evaluation nomogram of EHT. The area under the ROC curve of the nomogram was 0.722 (95% CI: 0.693-0.752; P<0.001) and 0.747 (95% CI: 0.690-0.804; P<0.001) for the training and validation set, respectively. Furthermore, the Hosmer-Lemeshow test indicated excellent calibration performance, yielding P values of 0.969 for the training set and 0.761 for the validation set. In our study, the rs662799 variant of the APOA5 gene was significantly associated with susceptibility to EHT. A nomogram for the early prediction of EHT in in the Chinese population was successfully constructed and validated. The nomogram can provide a visual assessment of the risk of EHT for clinical consultation.

Dark chocolate intake and cardiovascular diseases: a Mendelian randomization study

Previous intervention studies have shown some benefits of dark chocolate for the cardiovascular system, but it has not been established whether dark chocolate intake is associated with the risk of cardiovascular diseases (CVDs). To investigate the causality between dark chocolate intake and the risk of CVDs, a Mendelian randomization (MR) study was conducted. We obtained summary-level data on dark chocolate intake and CVDs from publicly available genome-wide association studies. In this MR study, the main approach was to use a fixed-effect model with inverse variance weighted (IVW) and evaluate the robustness of the results via sensitivity analysis. We found that dark chocolate intake was significantly associated with the reduction of the risk of essential hypertension (EH) (OR = 0.73; 95% CI 0.60–0.88; p = 1.06 × 10−3), as well as with the suggestive association to the reduced risk of venous thromboembolism (OR = 0.69; 95% CI 0.50–0.96; p = 2.81 × 10−2). However, no association was found between dark chocolate intake and the other ten CVDs. Our study provides evidence for a causality between dark chocolate intake and a reduced risk of EH, which has important implications for the prevention of EH in the population.

Association between copper intake and essential hypertension: dual evidence from Mendelian randomization analysis and the NHANES database.

Although previous studies have identified an association between trace elements and essential hypertension, the specific trace elements involved and the mechanisms of their association remain unclear. This study aimed to elucidate the relationship between various human trace elements and essential hypertension, thereby addressing existing gaps in the research. This study employed two-sample, multivariate, and inverse Mendelian randomization (MR) analyses to investigate the causal relationship between 15 human trace elements as exposure factors and essential hypertension as the outcome. The analysis revealed a statistically significant association between copper intake and essential hypertension. Further validation was conducted using logistic regression models based on data from the National Health and Nutrition Examination Survey (NHANES). Eighteen trace elements were initially identified through searches in the GWAS database and PubMed. After screening, 15 trace elements were selected as potential exposure factors. MR analysis, utilizing the 2021 genome-wide dataset for essential hypertension, identified copper as a risk factor, showing a positive association with hypertension. Subsequent logistic regression analyses based on NHANES data further confirmed a significant association between dietary copper intake and the risk of essential hypertension, except for the 0.80-1.08 mg/d group in model 3 (p < 0.05). Restricted cubic spline (RCS) analysis indicated a nonlinear relationship between copper intake and the risk of developing essential hypertension. This study demonstrates a significant association between copper intake and the development of essential hypertension. The findings suggest that higher copper intake is linked to an increased risk of hypertension, underscoring the need to monitor copper intake levels in the prevention and management of this condition.

The RAAS system SNPs polymorphism is associated with essential hypertension risk in rural areas in northern China.

Objectives: Epidemiological evidence has shown that genetics and environment are associated with the risk of hypertension. However, the specific SNP effects of a cluster of crucial genes in the RAAS system on the risk of hypertension are unclear. Methods: A case-control study was performed on the baseline participants of Environment and Chronic Disease in Rural Areas of Heilongjiang China (ECDRAHC) study. According to the inclusion and exclusion criteria, 757 subjects (428 hypertensive patients) were enrolled. A total of 32 SNP sites and related haplotypes, involved in AGT (angiotensinogen), ACE (angiotensin-converting enzyme), AGTR1, CYP11B2 (aldosterone-synthase), LDLR (low-density lipoprotein receptor), LRP5 (low-density lipoprotein receptor associated protein 5), LRP6 (low-density lipoprotein receptor associated protein 6), PPARG (peroxisome proliferator-activated receptor gamma) and ACE2 (angiotensin-converting enzyme 2) genes which exert important roles in renin-angiotensin-aldosterone system (RAAS) system were analyzed. Furthermore, a polygenic scoring model was established to assess individual risk of developing hypertension based on the comprehensive SNPs effects in genes related the RAAS system. Results: After controlling the impact of confounding factors, multivariate logistic regression analysis revealed that the distribution of AGT/rs5046, LRP6/rs12823243 and ACE2/rs2285666 was associated with susceptibility to essential hypertension. In genetic score model, the score > -0.225 had a higher risk, the OR (95%CI) was 1.229 (1.110, 1.362). Conclusions: To the best of our knowledge, this is the first time a hypertension risk scoring model on RAAS associated gene cluster has been constructed, which will provide a novel approach for prevention and control of essential hypertension.

Evaluation of the correlation between fetuin-B levels and essential hypertension: a cross-sectional study.

Fetuin-B, a cytokine that regulates lipid metabolism, has recently been linked to cardiovascular diseases such as coronary heart disease. In this study, we discussed the relationship between fetuin-B and essential hypertension. A bioinformatics analysis of fetuin-B was performed. A total of 206 with essential hypertension and 180 age- and-sex-matched healthy subjects were enrolled. Plasma fetuin-B, endothelin 1 (ET-1), nitric oxide (NO), and adiponectin (ADI) levels were measured using ELISA kits. Bioinformatics analysis has revealed that fetuin-B plays an important role in pathways such as lipid metabolism. Compared with healthy subjects, serum fetuin-B levels in patients with essential hypertension were significantly increased. Correlation analysis showed that the serum fetuin-B level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure, body mass index, fat percentage in vivo, waist-hip ratio, intima-media thickness, low-density lipoprotein cholesterol (LDL-C), glutamyltranspeptidase, alanine transaminase, albumin, fasting blood glucose (FBG), glycated hemoglobin, and ET-1 in the overall study subjects (all P < 0.05) and negatively correlated with HDL-C, ADI, and NO (all P < 0.05). Multivariate linear regression analysis showed that SBP, FBG, LDL-C, ADI, and ET-1 were independent factors affecting serum fetuin-B. A binary logistic regression analysis showed that fetuin-B was an independent risk factor for primary hypertension (odds ratio: 1.060, 95% CI: 1.034-1.086, P < 0.001). Receiver operating characteristic curve analysis was used to evaluate the predictive value of fetuin-B for primary hypertension, and the optimal cutoff point was 83.14 μg/mL (sensitivity 77.4%, specificity 63.3%) (area under the curve) = 0.7738, 95% CI 0.7276-0.8200, P < 0.001). Elevated fetuin-B levels are associated with an increased risk of essential hypertension.

Association of Interleukin-6 Genetic Polymorphisms (rs1800795, -174C > G and rs1800796, -572G > C) With Risk of Essential Hypertension in the Chinese Population.

Background Interleukin-6 (IL-6) plays a critical role in essential hypertension (EH) and cardiovascular disease. Evidence suggests two hotspot single nucleotide polymorphisms (SNPs) of theIL-6 gene (rs1800795, -174C > G and rs1800796, -572G > C) might be associated with the susceptibility of EH. However, no consensus has yet been established. Thus, we aimed to investigate the potential association between IL-6 gene polymorphisms and the risk of EH based on a case-control study in a Chinese population. Materials and methods A total of 479 subjects (272 healthy controls and 207 EH patients) were randomly enrolled in our study. After extracting the genomic DNA, two SNPs of theIL-6 gene (rs1800795, -174C > G and rs1800796, -572G > C) were genotyped to analyze the potential association between these genetic variants and EH risk. Multiple genetic models were performed to investigate the strength of association by calculating the odds ratio (OR) and 95% confidence interval (95% CI). The potential effect of SNPs on gene expression was evaluated using expression quantitative trait loci (eQTL) analysis. Results The genotyping findings of IL-6 rs1800795, -174C > Gpolymorphism showed threestudy participants with CG genotype and 204 with GG genotype in the EH patients.The IL-6-174C > G polymorphism was significantly associated with EH risk (P = 0.046) and conferred a reduced risk of EH development (OR = 0.99, 95%CI = 0.97-1.00). Conversely, no substantial association between IL-6 rs1800796, -572G > C polymorphism and the risk of EH was found in all genetic models (P > 0.05). Moreover, the eQTL analysis indicated that the -174C > G polymorphism was significantly associated with gene expression of IL-6 (P = 0.006), and the G allele corresponded to a reduced IL-6 gene expression (Beta = -0.397). Compared with -174C > G, the -572G > C polymorphism was not found to be significantly associated with IL-6 gene expression (Beta = -0.120, P = 0.560). Conclusions Our findings provide evidence that the rs1800795, -174C > G polymorphism can affect the expression levels of IL-6, and the risk of EH occurrence. However, the rs1800796, -572G > C polymorphism does not regulate the IL-6 gene expression levels and the susceptibility of EH.

Association study of WNK1 genetic variants and essential hypertension risk in the Northern Han Chinese in Beijing.

Background: Essential hypertension (EH) is a complex disorder resulting from interaction of genetic and environmental factors. Lysine deficient protein kinase 1 (WNK1) plays a very important role in maintaining renal potassium, sodium and chlorine ions balance as well as the regulation of blood pressure, so the WNK1 gene is considered a key gene for EH. This study thus sought to evaluate possible genetic associations between the WNK1 genetic variants and EH risk in the Northern Han Chinese population in Beijing. Methods: This study included 476 hypertensive subjects and 491 normotensive subjects. A total of 12 tag SNVs of WNK1 gene were genotyped successfully by TaqMan assay. Comparisons of the genotypic and allelic frequency between cases and controls were made by using the chi-square test. Logistic regression analyses were performed under different genetic models, and haplotype analysis was also conducted. Results: A total of 12 SNVs were identified as the tag SNVs for WNK1 gene. Significant associations were observed between WNK1 gene rs7305099 variant and EH risk, and T allele influenced hypertension risk in a protective manner. After correcting for multiple testing using Bonferroni, the significance remained for the SNV of rs7305099 in three genetic models [allele comparison, p < 0.0002, OR = 0.627, 95%CI (0.491-0.801); homozygote comparison, p < 0.0003, OR = 0.278, 95%CI (0.140-0.552); additive model, p < 0.0003, OR = 0.279, 95%CI (0.140-0.553)]. In the haplotype analyses, we found that the haplotype A-A-A-C-G-G-G was significantly associated with increased risk for EH (p = 0.043, OR = 1.23). Conclusion: Our data suggested that the rs7305099 genetic variant and the haplotype A-A-A-C-G-G-G on WNK1 gene might be associated with the susceptibility of EH in the Northern Han Chinese population. These could provide evidences to the risk assessment, early prevention and individualized therapy of EH to some extent.

GENETIC ASSOCIATION STUDY BETWEEN T-786C NOS3 POLYMORPHISM AND ESSENTIAL HYPERTENSION IN AN ALGERIAN POPULATION OF THE ORAN CITY

Objective: We aim in this study to analyze the relationship between NOS3 -786T/C, a common genetic variant and HTN in a sample of the Algerian population of the Oran city. Design and method: A case-control study has been performed on 154 subjects including 77 hypertensives and 77 normotensives. The recruitment of these subjects was done in local Health Centers of the city of Oran, West Algeria. Consent was obtained from all participants. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to genotype the NOS -786T/C variant. Results: The distribution of the allelic frequencies did not differ between cases and controls. However, after adjustment with the age, sex, and body mass index, we observed a significant association between NOS -786C allele and HTN status. Conclusions: Our results indicate that the C allele of the NOS3 gene is associated with an increased risk of essential hypertension in this sample of the Algerian population of Oran city.

Types of milk consumed and risk of essential hypertension: A 2-sample Mendelian randomization analysis

Observational associations between milk consumption and essential hypertension have been reported. However, their causal inferences have not been proven, and the effects of different types of milk consumption on hypertension risk remain poorly characterized. The Mendelian randomization (MR) analysis was performed using public summary-level statistics from genome-wide association studies to determine whether the different types of milk consumption affect essential hypertension differently. Six different milk consumption types were defined as exposure conditions, whereas essential hypertension identified by the ninth and tenth revisions of the International Classification of Diseases was considered the outcome of interest. Genetic variants, which were genome-wide associated with the types of milk consumed, were used as an instrumental variable for MR analysis. In primary MR analysis, the inverse-variance weighted method was adopted followed by several sensitivity analyses. Our findings suggested that of the 6 common types of milk consumed, semi-skimmed and soya milk products were protective against essential hypertension, whereas skim milk had the opposite effect. Consistent results were also observed in sensitivity analyses that followed. The present study provided genetic evidence that a causal link between milk consumption and the risk of essential hypertension and a new reference for the diet antihypertensive treatment plan for patients with hypertension.

INSR and ISR‑1 gene polymorphisms and the susceptibility of essential hypertension: A meta‑analysis.

INSR and ISR-1 may be candidate genes for essential hypertension (EH). However, the genetic association between the INSR and ISR-1 gene polymorphisms and EH risk remains contradictory. To determine a more precise association of the INSR and ISR-1 gene polymorphisms and EH, the present study performed a meta-analysis. Eligible studies up to Jan 2021 were retrieved from multiple databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the genetic associations between the allele, dominant and recessive models of INSR Nsil, RsaI and ISR-1 G972R polymorphisms and EH susceptibility. A total of 10 case-control studies encompassing 2,782 subjects including 1,289 cases and 1,493 controls were evaluated for the present meta-analysis. Neither of the allele, dominant and recessive models of INSR Nsil and ISR-1 G972R polymorphisms was associated with EH risk (P>0.05). While the allele [P=0.0008, OR=0.58, (95% CI)=(0.42, 0.80)], dominant [P=0.02, OR=0.59, (95% CI)=(0.38, 0.92)] and recessive models [P=0.003, OR=0.38, (95% CI)=(0.20, 0.72)] of INSR Rsal polymorphism were associated with decreased risk of EH. Subgroup analysis according to ethnicity showed that the significant associations between the allele, dominant and recessive models of INSR Rsal polymorphism and EH risk were observed in Caucasian populations, but not in Asian populations (P>0.05). In conclusion, the INSR Rsal polymorphism is probably a protective factor for EH. To identify the result, additional case-control designed research with larger numbers of subjects are required.

Association of APP gene polymorphisms and promoter methylation with essential hypertension in Guizhou: a case–control study

BackgroundSingle-nucleotide polymorphisms (SNPs) and DNA methylation are crucial regulators of essential hypertension (EH). Amyloid precursor protein (APP) mutations are implicated in hypertension development. Nonetheless, studies on the association of APP gene polymorphism and promoter methylation with hypertension are limited. Therefore, this case–control aims to evaluate the genetic association of APP gene polymorphism and promoter methylation with EH in Guizhou populations.Objective and methodsWe conducted a case–control study on 343 EH patients and 335 healthy controls (including Miao, Buyi, and Han populations) in the Guizhou province of China to analyze 11 single-nucleotide polymorphisms (rs2040273, rs63750921, rs2211772, rs2830077, rs467021, rs368196, rs466433, rs364048, rs364051, rs438031, rs463946) in the APP gene via MassARRAY SNP. The MassARRAY EpiTYPER was employed to detect the methylation levels of the promoters.ResultsIn the Han population, the rs2211772 genotype distribution was significantly different between disease and control groups (χ2 = 6.343, P = 0.039). The CC genotype reduced the risk of hypertension compared to the TT or TC genotype (OR 0.105, 95%CI 0.012–0.914, P = 0.041). For rs2040273 in the Miao population, AG or GG genotype reduced the hypertension risk compared with the AA genotype (OR 0.533, 95%CI 0.294–0.965, P = 0.038). Haplotype TCC (rs364051–rs438031–rs463946) increased the risk of EH in Guizhou (OR 1.427, 95%CI 1.020–1.996, P = 0.037). Each 1% increase in CpG_19 (− 613 bp) methylation level was associated with a 4.1% increase in hypertension risk (OR 1.041, 95%CI 1.002–1.081, P = 0.039). Each 1% increase in CpG_1 (− 296 bp) methylation level was associated with an 8% decrease in hypertension risk in women (OR 0.920, 95%CI 0.860–0.984, P = 0.015). CpG_19 significantly correlated with systolic blood pressure (r = 0.2, P = 0.03). The methylation levels of CpG_19 in hypertensive patients with rs466433, rs364048, and rs364051 minor alleles were lower than that with wild-type alleles (P < 0.05). Moreover, rs467021 and rs364051 showed strong synergistic interaction with EH (χ2 = 7.633, P = 0.006). CpG_11, CpG_19, and rs364051 showed weak synergistic interaction with EH (χ2 = 19.874, P < 0.001).ConclusionIn summary, rs2211772 polymorphism and promoter methylation level of APP gene may be linked to EH in Guizhou populations. Our findings will provide novel insights for genetic research of hypertension and Alzheimer's disease.

Genetic polymorphisms of purinergic P2Y2 receptor were associated with the susceptibility to essential hypertension in Chinese postmenopausal women.

Hypertension has become a prominent public health concern. Essential hypertension (EH) is a polygenic disorder caused by multiple susceptibility genes. It has been previously shown that the purinergic P2Y2 receptor (P2Y2R) regulates blood pressure; however, whether P2Y2R genetic polymorphisms correlate with EH has not been investigated in Chinese. Our study included 500 EH cases and 504 controls who are Chinese postmenopausal women. We used allele-specific polymerase chain reaction (ASPCR) to genotype five single-nucleotide polymorphism (SNPs) in the P2Y2R gene, i.e., rs4944831, rs12366239, rs1783596, rs4382936, and rs10898909. We assessed the association of P2Y2R genetic polymorphisms with EH susceptibility. The results demonstrated that P2Y2R rs4382936A was correlated with a high risk of EH; particularly, the participants with the rs4382936A allele and CA/AA/(CA+AA) genotypes were at higher risks to EH compared to the subjects with the rs4382936C allele and CC genotype. Moreover, haplotype CAG combined by rs1783596-rs4382936-rs10898909 was a susceptible haplotype for EH, whereas haplotype CCG was a protective haplotype for EH. These results may provide new evidence for applying P2Y2R genetic polymorphisms as useful markers in clinic screening or monitoring potential EH cases in a population of Chinese postmenopausal women.

Serum creatinine to bilirubin ratio associated with essential hypertension.

Previous studies have shown that serum bilirubin (BIL) is significantly decreased, and serum creatinine (Cr) level is increased in patients with essential hypertension (EH). In this paper, the ratio of serum Cr to BIL was measured to explore whether the ratio was associated with EH risk. 80 EH cases were selected as the observation group. 44 cases with normal blood pressure were selected as the control group. Serum Cr and BIL levels were detected, and the ratio values were calculated. Compared with the control group, the Cr to total bilirubin (TBIL) ratio (Cr/TBIL, CTR), Cr to direct bilirubin (DBIL) ratio (Cr/DBIL, CDR) and Cr to indirect bilirubin (IBIL) ratio (Cr/IBIL, CIR) in the EH group were significantly increased (p<0.05). Spearman correlation analysis showed that EH risk was positively correlated with CTR and CIR, while it was negatively correlated with serum BIL (p<0.05). The area under the ROC curve of CTR, CDR and CIR in diagnosing EH were 0.719 (95% CI: 0.631-0.796) (p<0.001), 0.700 (95% CI: 0.611-0.779) (p<0.001) and 0.716 (95% CI: 0.628-0.793) (p<0.001), respectively. Logistic regression analysis showed that CTR, CDR and CIR were independent risk factors for EH (CTR OR: 1.28, 95% CI: 1.11-1.48, p=0.0008), (CDR OR: 1.03, 95% CI: 1.003-1.067, p=0.032), (CIR OR: 1.17, 95% CI: 1.07-1.29, p=0.001). CTR and CIR are positively correlated with the incidence of EH. With the increase of blood pressure, CTR and CIR increase. CTR and CIR are independent risk factors for the incidence of EH.

Relationship of Toll-Like Receptors 2 and 4 Gene Polymorphisms with Essential Hypertension in Chinese Han Population

Objective: There are numerous studies suggesting that genetic polymor-phisms of inflammation factors Toll-like receptors 2 and 4 (TLR2, TLR4) might play a role in the pathophysiological process of hypertension. In this study, we evaluated the association in a sample of members of the Chinese Han population. Method: We selected four single nucleotide polymor-phisms (SNP) of TLR2 (rs3804099, rs3804100, rs7656411) and TLR4 (rs1927906) genes, and measured the distributions of genotypic and allelic frequencies in 1063 participants, including 391 essential hypertension pa-tients and 672 controls. Result: No significant differences in the genotypic and allelic frequencies of the four SNPs were detected between cases and controls. However, three haplotypes, CCG, TTG and TTT of TLR2, were significantly associated with a decrease in the risk of essential hyperten-sion (OR: 0.512, 95% CI: 0.397 - 0.660, P P = 0.0038; OR: 0.797, 95% CI: 0.667 - 0.952, P = 0.0122, respectively). Inversely, the risk of essential hypertension increased sig-nificantly in patients with the CTG, TCG or TCT haplotypes (OR: 2.924, 95% CI: 2.157 - 3.963, P P P TLR2 might have profound effects on the development of essential hypertension in the Chinese Han population.

Polymorphisms in the Renin-Angiotensin System and eNOS Glu298Asp Genes Are Associated with Increased Risk for Essential Hypertension in a Mexican Population.

Essential hypertension is the result of modifiable and genetic factors, and it is associated with increased risk for atherothrombosis. Some polymorphisms are associated with hypertensive disease. The objective was to analyze the association between eNOS Glu298Asp, MTHR C677T, AGT M235T, AGT T174M, and A1166C and ACE I/D polymorphisms with essential hypertension in the Mexican population. In the present study, 224 patients with essential hypertension and 208 subjects without hypertension were included. The Glu298Asp, C677T, M235T, T174M, A1166C, and I/D polymorphisms were determined by the PCR-RFLP technique. We found statistical differences in age, gender, BMI, systolic and diastolic blood pressure, and total cholesterol between control and cases. However, we found no significant differences in HbA1c and triglycerides between both groups. We observed statistical significant differences in the genotype distribution of Glu298Asp (P = 0.001), I/D (P = 0.02), and M235T (P = 0.004) polymorphisms between both groups. In contrast, there were no differences related to distribution of genotypes of MTHFR C677T (P = 0.12), M174T (P = 0.46), and A1166C (P = 0.85) between cases and control groups. We identified that Glu298Asp, I/D, and M234T polymorphisms represented an increased risk for essential hypertension and those genetic variants could contribute to the presence of endothelial dysfunction and vasopressor effect, hyperplasia, and hypertrophy of smooth muscle cells, which had an impact for hypertension. In contrast, we found no association between C677C, M174T, and A1166C polymorphisms and hypertensive disease. We suggested that those genetic variants could be identified in individuals with high risk to avoid hypertension and thrombotic disease.

The association of plasma sortilin with essential hypertension and subclinical carotid atherosclerosis: A cross-sectional study.

BackgroundSortilin, a protein that regulates glucose and lipid metabolism, has recently been linked to cardiovascular diseases (CVDs) such as coronary heart disease and carotid artery stenosis. In this study, we measured circulating sortilin concentrations in essential hypertensive (EH) patients, and evaluated the association between sortilin, hypertension, and subclinical carotid atherosclerosis in hypertensive individuals.MethodsThis cross-sectional study included 336 individuals, including 186 newly diagnosed EH patients and 150 age-and-sex-matched normotensive healthy subjects (NT). Plasma sortilin and adiponectin (ADI) levels were measured using ELISA kits. In the EH group, high-resolution B-mode ultrasound was used to detect the existence of subclinical carotid atherosclerosis (subAS), which was defined as having a carotid intima–media thickness (cIMT) ≥ 1.0 mm and/or plaque on the carotid artery without any clinical manifestations.ResultsOur findings showed that plasma sortilin concentrations ranged from 3.34–11.34 ng/ml for all subjects. Sortilin levels were significantly higher in the EH group than in the NT group (8.10 ± 1.82 ng/ml vs. 6.37 ± 1.52 ng/ml, P < 0.001) and were further upregulated in the EH with subclinical carotid atherosclerosis (EH + subAS) group compared to the EH without subclinical carotid atherosclerosis (EH-subAS) group (8.42 ± 1.75 ng/ml vs. 7.79 ± 1.84 ng/ml, P < 0.05). In correlation analysis, sortilin was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), white blood cell (WBC), endothelin-1 (ET-1), high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and cIMT (all P < 0.05) and negatively associated with NO and ADI (P < 0.001). Multiple linear regression analysis revealed that SBP, LDL-C, and ET-1 were independently associated with plasma sortilin levels. Increased sortilin levels were independently associated with the risk of EH (OR: 1.86, 95%CI: 1.56–2.20, P < 0.001) and EH + subAS (OR: 1.33, 95%CI: 1.07–1.66, P = 0.011), after adjustment for multiple risk factors. Restricted spline curve showed that elevated sortilin levels increase the odds of having EH.ConclusionElevated sortilin levels are associated with an increased risk of essential hypertension and subclinical carotid atherosclerosis in hypertensive patients.