Clinical and genetic analysis of essential hypertension with CYB gene m.15024G>A mutation. / 携带CYB m.15024G>Açªå˜çš„åŽŸå‘æ€§é«˜è¡€åŽ‹å®¶ç³»é—ä¼ å­¦åˆ†æž.

OBJECTIVES: To explore the role of mitochondrial CYB 15024G>A mutation in the development of essential hypertension. METHODS: Mitochondrial genome sequences of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with mitochondrial CYB 15024G>A mutation and its pedigree were analyzed. Lymphocytes derived from patient and family members were transformed into immortalized lymphoblastoid cell lines, and the levels of adenosine triphosphate (ATP), mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected. RESULTS: The penetrance of this essential hypertension family was 42.9%, and the age of onset was 46-68 years old. Mitochondrial genome sequencing results showed that all maternal members carried a highly conserved mitochondrial CYB 15024G>A mutation. This mutation could affect the free energy of mitochondrial CYB for secondary and tertiary structure and protein folding, thereby changing its structural stability and the structure of the electron transfer function area around the mutation site. Compared with the control, the cell line carrying the mitochondrial CYB 15024G>A mutation showed significantly decreased levels of mitochondrial CYB, ATP and mitochondrial membrane potential, and increased levels of ROS (P<0.01). CONCLUSIONS: Mitochondrial CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, leading to cell dysfunction, which suggests that the mutation may play a synergistic role in essential hypertension.

Dopamine Receptor D1R and D3R and GRK4 Interaction in Hypertension.

Essential hypertension is caused by the interaction of genetic, behavioral, and environmental factors. Abnormalities in the regulation of renal ion transport cause essential hypertension. The renal dopaminergic system, which inhibits sodium transport in all the nephron segments, is responsible for at least 50% of renal sodium excretion under conditions of moderate sodium excess. Dopaminergic signals are transduced by two families of receptors that belong to the G protein-coupled receptor (GPCR) superfamily. D1-like receptors (D1R and D5R) stimulate, while D2-like receptors (D2R, D3R, and D4R) inhibit adenylyl cyclases. The dopamine receptor subtypes, themselves, or by their interactions, regulate renal sodium transport and blood pressure. We review the role of the D1R and D3R and their interaction in the natriuresis associated with volume expansion. The D1R- and D3R-mediated inhibition of renal sodium transport involves PKA and PKC-dependent and -independent mechanisms. The D3R also increases the degradation of NHE3 via USP-mediated ubiquitinylation. Although deletion of Drd1 and Drd3 in mice causes hypertension, DRD1 polymorphisms are not always associated with human essential hypertension and polymorphisms in DRD3 are not associated with human essential hypertension. The impaired D1R and D3R function in hypertension is related to their hyper-phosphorylation; GRK4γ isoforms, R65L, A142V, and A486V, hyper-phosphorylate and desensitize D1R and D3R. The GRK4 locus is linked to and GRK4 variants are associated with high blood pressure in humans. Thus, GRK4, by itself, and by regulating genes related to the control of blood pressure may explain the "apparent" polygenic nature of essential hypertension.

Association between Interactions among ACE Gene Polymorphisms and Essential Hypertension in Patients in the Hefei Region, Anhui, China.

Objective: Essential hypertension (EH) is a common cardiovascular disease that endangers human health. Its pathogenesis is complex and has not been fully elucidated. We explore the association between EH and interactions among polymorphisms of the angiotensin converting enzyme (ACE) gene in the Hefei region, Anhui, China. Methods: A total of 500 participants (400 hypertensive and 100 normotensive) were included in this study. The polymorphisms were detected via improved multiple ligase detection reaction (iMLDR). To improve the accuracy of prediction, multifactor dimensionality reduction (MDR) was used to analyze the overall effect of interactions among seven loci on the incidence of EH. Results: The frequencies of polymorphisms in the ACE genes rs12709426, rs4291, rs4309, rs4331, rs4343, rs4459609, and rs4461142 in the EH group were not statistically significantly different from those in the control group. We also found that the single nucleotide polymorphism (SNP) rs12709426 only had a homozygous AA genotype and no polymorphisms. There were no differences in the frequency of genetic polymorphisms between the EH and control groups. The best model explaining the EH group was the combined effect of ACE genes rs4291, rs4309, and rs4461142. Conclusion: There is an interaction effect among ACE gene loci in EH patients in Hefei region, Anhui, China. Also, the ACE gene SNP rs12709426 only has a homozygous AA genotype and does not show an association with EH.

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

BACKGROUND: Single-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 METHODS: We 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. RESULTS: In 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). CONCLUSION: In 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.

Contribution of NOS3AS Variants to Susceptibility to Essential Hypertension: A Study in Kermanshah Province, Western Iran.

Hypertension (HTN) is a global health challenge and increase the risk of cardiovascular disease. Hypertension has a multifactorial course of evolution, with both genetic and environmental factors playing an important role. To date, a number of genes and pathways have been proposed to be associated with HTN, among which is Nitric Oxide pathway. NO levels can be regulated by reactive oxygen species (ROS), superoxide and post-transcriptional mechanisms, including sense-anti sense interactions. NOS3AS gene encodes an antisense RNA (sONE) which is complementary to NOS3 transcript in 662 nucleotides and may regulate NOS3 in a post-transcriptional manner. In this study, we sought to define the role of NOS3AS in the pathophysiology of essential HTN. A total of 131 cases with hypertension and 115 controls were enrolled in the study. Peripheral blood was drawn from all study participants after signing the informed consent form. Three variants (rs71539868, rs12666075 and rs7830) were investigated by Tetra-ARMS PCR method. The results were then statistically analyzed. We found statistically significant association between rs7830 TT genotype, rs12666075 GT and TT genotypes with susceptibility to HTN. We failed to observe association between rs71539868 and susceptibility to HTN. The present study showed a strong association between NOS3AS variants and susceptibility to hypertension in the population of Kermanshah province. Our results may shed more light on the mechanisms of disease development and may also help to better identify genetic predispositions and individuals at risk.

Insulin receptor substrate-1 gene polymorphism and lipid panel data in type 2 diabetic patients with comorbid obesity and/or essential hypertension.

Objective. The hallmarks of type 2 diabetes mellitus (T2DM) are insulin resistance (IR) and insulin receptor substrate (IRS) proteins essential for the insulin signaling. IRS-1 gene has not only been shown to be associated with T2DM, but also has indicated that it may significantly correlate with diabetic complications, such as coronary heart disease and obesity. The aim of this study was to evaluate changes of the lipid panel data in T2DM patients with comorbid obesity and/or essential hypertension in connection with the IRS-1 (rs2943640) polymorphism. Methods. The study involved 33 T2DM patients and 10 healthy individuals. The IRS-1 (rs2943640) polymorphism was genotyped using a TaqMan real-time polymerase chain reaction method. Blood serum lipid panel data were determined with commercially available kits using a Cobas 6000 analyzer. Results. Analysis of the serum lipid panel data depending on the presence of the C/A alleles of IRS-1 (rs2943640) polymorphism in T2DM patients, regardless of the presence/absence of comorbidities, showed significantly lower level of high-density lipoprotein cholesterol (HDL-C) and significantly higher level of non-HDL-C in the carriers of C allele vs. carriers of A allele. In T2DM patients with comorbid obesity and essential hypertension, proatherogenic lipid changes were found in both C and A alleles carriers. Analysis of the effect of IRS-1 (rs2943640) genotypes on serum lipid panel data in T2DM patients, regardless of the presence/absence of comorbidities, showed that the CC genotype carriers had more pronounced pro-atherogenic changes vs. carriers of СА and АА genotypes. In the comorbid course of T2DM (both in combination with obesity and obesity and essential hypertension), pro-atherogenic changes were found in the carriers of the CA genotype of IRS-1 (rs2943640) polymorphism. Conclusions. The presence of the C allele of IRS-1 (rs2943640) polymorphism in both homo-zygous and heterozygous states indicates increased risk of pro-atherogenic changes in T2DM patients with comorbid obesity and/or essential hypertension.

Polymorphism of NOS3 gene and its association with essential hypertension in Guizhou populations of China.

OBJECTIVE: A case-control study was conducted to evaluate the relationship between endothelial nitric oxide synthase (NOS3) gene polymorphism and essential hypertension in the Han, Miao, and Buyi populations in Guizhou China. METHODS: DNA was collected from the blood samples of 353 essential hypertension patients and 342 healthy controls from Guizhou province of China. Eight polymorphisms of the NOS3 gene were genotyped using the Sequenom MassARRAY platform. For genetic analysis, SPSS 26.0, Haploview, SNPStats, SHEsis, and MDR were utilized. RESULTS: All SNPs (rs11771443, rs1808593, rs753482, rs3918186, rs3918188, rs3918227, rs7830, and rs891512) satisfied the Hardy-Weinberg equilibrium test (P > 0.05). The allele and genotype frequencies of rs7830 and rs1808593 in case-control groups demonstrated significant differences (P < 0.05). Compared to the TT genotype of rs1808593, the TG or GG genotype reduced the risk of hypertension in the Miao population (OR = 0.410, 95% CI: 0.218-0.770, P = 0.006). Compared to the GG or GT genotype of rs7830, the TT genotype increased the risk of hypertension in the overall populations (OR = 1.716, 95%CI: 1.139-2.586, P = 0.010). The CATT (rs3918227-rs391818186-rs1808593-rs7830) haplotype was a risk factor for hypertension in the Miao and Han populations (OR = 1.471, 95%CI: 1.010-2.143, P = 0.044 and OR = 1.692, 95%CI: 1.124-2.545, P = 0.011). The CAGG haplotype in the Miao population was a protective factor against hypertension (OR = 0.555, 95%CI: 0.330-0.934, P = 0.025). The rs3918188, rs1808593, and rs7830 in the Miao population showed an interaction effect on hypertension (P < 0.001). The rs11771443, rs3918188, and rs7830 in the Buyi and Han populations showed an interaction effect on hypertension (P = 0.013 and P < 0.001). CONCLUSION: The single nucleotide polymorphisms rs1808593 and rs7830 of NOS3 gene are associated with essential hypertension in Guizhou ethnic populations.

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

Background: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.

Association of Circular RNAs levels in blood and Essential Hypertension with Carotid Plaque.

BACKGROUND: As one of the essential hypertension (EH)-mediated target organ damage, carotid plaque is a crucial subclinical precursor for cardiovascular events. Therefore, it is vital to identify the risk factors and pathogenesis for EH with carotid plaque. METHODS: Based on our previous microarray analysis, we selected four circRNAs as the candidate circRNAs and detected their expression levels in blood of 192 subjects (64 healthy controls, 64 EH patients, and 64 EH patients with carotid plaque) by qRT-PCR analysis. The regulatory mechanism of circRNAs involved in carotid plaque was predicted by bioinformatics analysis. RESULTS: The level of hsa_circ_0124782 increased significantly and the levels of hsa_circ_0131618 and hsa_circ_0127342 decreased significantly in the EH group and EH with carotid plaque group compared with the control group (P < .05). Functional enrichment analysis showed that three circRNAs might be implicated in pathogenesis for carotid plaque. CONCLUSION: Our study revealed the relationship between three circRNAs and carotid plaque, suggesting that they may serve as potential biomarkers for EH with carotid plaque.

Novel mitochondrial tRNALeu(UUR) 3261A > g mutation in two pedigrees with essential hypertension.

BACKGROUND: Essential hypertension (EH) was associated with mitochondrial tRNA mutations. AIMS: This study was designed to assess the association between EH and mitochondrial dysfunction. METHODS: A total of 30 individuals from two different Chinese families exhibit maternally inherited EH were assessed for genetic, clinical, and biochemical phenotypes pertaining to EH and mitochondrial functionality. These analyses included assessments of tRNALeu(UUR) 3261A > G mutation status, mitochondrial membrane permeability, mitochondria-associated ATP and reactive oxygen species (ROS) generation, and electron transport chain functionality. RESULTS: EH was detected in 6 total analyzed members of the two families assessed in the present study, with its initial age of onset and presentation varying among patients. These patients with EH exhibited the tRNALeu(UUR) 3261A > G mutation and were of the B5 and D4 Eastern Asian mitochondrial haplogroups. This 3261A > G mutation was predicted to result in disruption of normal tRNALeu(UUR) activity owing to the destabilization of conserved base pairing (30A-40U). Consistent with this prediction, we found that cybrid cell lines exhibiting this 3261A > G mutation exhibited a ~49.05% decrease in baseline tRNALeu(UUR) levels. These cells additionally exhibited ~44.81% reductions in rates of mitochondrial translation. CONCLUSIONS: To facilitate future molecular diagnosis, the 3261A > G mutation should be included in the list of hereditary risk factors. Our findings will aid in the counseling of EH families.

Association between AT1 receptor gene polymorphism and left ventricular hypertrophy and arterial stiffness in essential hypertension patients: a prospective cohort study.

BACKGROUND: AT1 receptor gene (AGTR1) is related to essential hypertension (EH), and left ventricular hypertrophy (LVH) and arterial stiffness are common complications of EH. This study aimed to explore the association between AGTR1 genotype and LVH and arterial stiffness in EH patients. METHODS: A total of 179 EH patients were recruited in this study. Oral exfoliated cells were collected from each patient, and the genetic polymorphism of AGTR1(rs4524238) was assessed using a gene sequencing platform. The outcomes were LVH and arterial stiffness. RESULTS: Among 179 patients, 114 were with AGTR1 genotype of GG (57 males, aged 59.54 ± 13.49 years) and 65 were with AGTR1 genotype of GA or AA (36 males, aged 61.28 ± 12.79 years). Patients with AGTR1 genotype of GG were more likely to have LVH (47 [41.23%] vs. 14 [21.54%], P = 0.006) and arterial stiffness (30 [26.32%] vs. 8 [12.31%], P = 0.036). The AGTR1 polymorphism frequency was in accordance with Hardy-Weinberg equilibrium (P = 0.291). The multivariate logistic regression showed that AGTR1 genotype of GA or AA was independently associated with lower risk of LVH (OR = 0.344, 95%CI 160~0.696, P = 0.003) and arterial stiffness (OR = 0.371, 95%CI 0.155~0.885, P = 0.025) after adjusting for gender, age, and diabetes. CONCLUSION: EH patients with the AGTR1 genotype of GA or AA were at lower risk for LVH and arterial stiffness than those with the GG genotype.

Association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with risk of hypertension among the Ethiopian population.

INTRODUCTION: Although the pathophysiological mechanism of hypertension is not fully elucidated yet, a large number of pieces of evidence have shown that genetic alterations in the renin-angiotensin-aldosterone system play a central role. However, the association of insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene with essential hypertension is controversial yet, and there is a limited number of publications among the Ethiopian population. Therefore, this study aimed to determine the association of ACE gene I/D polymorphism with the risk of hypertension among essential hypertension patients at the University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia. MATERIALS AND METHODS: A case-control study was conducted from October 07, 2020, to June 02, 2021, among hypertensive patients and normotensive control groups at the University of Gondar Comprehensive Specialized Hospital. A structured questionnaire was used to collect socio-demographic data and anthropometric measurements. Five milliliters of blood were drawn from each of the randomly selected 64 hypertensive and 64 normotensive participants for molecular test analysis. Genetic polymorphism of the ACE gene was identified using polymerase chain reaction (PCR) and electrophoresis. Data analysis was done using SPSS version 25.0 software. The strength of association between the genotype and hypertension was estimated through the calculation of adjusted odds ratio and 95% confidence intervals using logistic regression. P-value < 0.05 was considered statistically significant. RESULT: The distribution of DD genotypes and D allele of the ACE gene were 48.4% and 63% in essential hypertensive patients, respectively, while it were 29.7% and 42.2% in control subjects respectively. The ACE DD genotype (p-value = 0.005) and D allele (p-value = 0.001) were more frequent among hypertensive patients as compared to controls. CONCLUSION: The present study found that the DD genotype and D allele of the ACE gene has had a strong association with a high risk of hypertension in the study population.

Efficacy of felodipine and enalapril in the treatment of essential hypertension with coronary artery disease and the effect on levels of Salusin-ß, Apelin, and PON1 gene expression in patients.

This study aimed to analyze the effect of felodipine combined with enalapril in the treatment of patients with essential hypertension and coronary artery disease. Also, the effect of these medicines was evaluated on the peripheral blood Salusin-ß, Apelin levels, and PON1 gene expression. For this purpose, 110 patients with essential hypertension combined with coronary heart disease, admitted to the hospital from January 2019 to January 2021, were selected and randomly divided into two groups. The control group was given felodipine treatment alone, and the study group was treated with combined application of felodipine and enalapril. The treatment effect, peripheral blood Salusin-ß, Apelin, PON1 gene expression, and the safety of medication were compared between the two groups. The results showed that the post-treatment systolic blood pressure in the study group was 119.77 ± 5.23 mm Hg and diastolic blood pressure was 86.84 ± 5.42 mm Hg, both of which were significantly lower than those in the control group (127.81 ± 6.92 mm Hg and 95.13 ± 6.08 mm Hg), with statistically significant differences (p<0.05). The effective rates of the study group and the control group were 92.73% and 74.54% respectively, with statistically significant differences (P<0.05). The post-treatment peripheral blood Salusin-ßlevel in the study group was 3.77±0.53mmol/L, and Apelin was 1.94±0.58µg/L, with statistically significant differences compared to the control group (P<0.05). The PON1 gene expression in the study group was higher than those in the control group after treatment (P<0.05). Also, the results showed that there was no statistical difference in adverse reactions between the two groups (P>0.05). According to these results, the combination of felodipine and enalapril in patients with essential hypertension combined with coronary artery disease can effectively lower the patients' blood pressure and improve their peripheral blood Salusin-ß, Apelin levels, and PON1 gene expression, thus enhancing the patients' therapeutic effect with few adverse effects and high safety.

The association between Alu hypomethylation and the severity of hypertension.

INTRODUCTION: Epigenetic changes that cause genomic instability may be the basis of pathogenic processes of age-associated noncommunicable diseases (NCDs). Essential hypertension is one of the most common NCDs. Alu hypomethylation is an epigenetic event that is commonly found in elderly individuals. Epigenomic alterations are also found in age-associated NCDs such as osteoporosis and diabetes mellitus. Alu methylation prevents DNA from being damaged. Therefore, Alu hypomethylated DNA accumulates DNA damage and, as a result, causes organ function deterioration. Here, we report that Alu hypomethylation is a biomarker for essential hypertension. RESULTS: We investigated Alu methylation levels in white blood cells from normal controls, patients with prehypertension, and patients with hypertension. The hypertension group possessed the lowest Alu methylation level when classified by systolic blood pressure and diastolic blood pressure (P = 0.0002 and P = 0.0088, respectively). In the hypertension group, a higher diastolic blood pressure and a lower Alu methylation level were observed (r = -0.6278). Moreover, we found that changes in Alu hypomethylation in the four years of follow-up in the same person were directly correlated with increased diastolic blood pressure. CONCLUSIONS: Similar to other age-associated NCDs, Alu hypomethylation is found in essential hypertension and is directly correlated with severity, particularly with diastolic blood pressure. Therefore, Alu hypomethylation may be linked with the molecular pathogenesis of high blood pressure and can be used for monitoring the clinical outcome of this disease.

Association of Endothelin-Converting Enzyme and Endothelin-1 Gene Polymorphisms with Essential Hypertension in Malay Ethnics.

Objectives: Endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, generated by enzymatic cleavage catalyzed by an endothelin-converting enzyme (ECE), plays a significant role in the regulation of hypertension. Methods: This study investigates the effect of endothelin-1 (Lys198Asn/rs5370) and ECE (rs212526 C/T) gene polymorphisms with essential hypertension (EH) among Malay ethnics. To determine the association of gene polymorphism, 177 hypertensives and controls (196) were genotyped using Taqman method. Results: A significant difference was observed in ET-1 rs5370 and ECE rs212526 gene polymorphisms between EH and control subjects (P < 0.001). A significantly high body mass index (BMI), waist-to-hip ratio, fasting plasma glucose, hemoglobin A1c, systolic and diastolic blood pressure, and lipid profiles were observed among the EH patients when compared to controls (P < 0.05). Moreover, T allele (rs5370) carriers in males have a high risk for EH. There was no significant association between gender in ECE C/T polymorphisms (P > 0.05). Conclusion: Based on our result, it is evident that the T allele of ET-1 rs5370 polymorphism and C allele of ECE rs212526 have a significant genetic risk factor in EH among Malay subjects, and BMI and age are associated with hypertension.

Methylenetetrahydrofolate Reductase Gene rs1801133 and rs1801131 Polymorphisms and Essential Hypertension Risk: A Comprehensive Analysis.

Background: Essential hypertension (EH) is a common and multifactorial disorder that is likely to be influenced by multiple genes. The methylenetetrahydrofolate reductase (MTHFR) gene rs1801133 and rs1801131 polymorphisms influence MTHFR enzyme activity and plasma homocysteine concentration. In addition, variations in MTHFR functions likely play roles in the etiology of EH. Thus far, a large number of studies investigating the associations between the MTHFR polymorphisms and EH have provided controversial or inconclusive results. To better assess the purported relationship, we performed a comprehensive analysis of 52 published studies. Objective and Methods. Eligible studies were identified by searching the PubMed, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the potential association between the MTHFR rs1801133 polymorphism and EH. Results: Overall, 10712 patients and 11916 controls were involved; we observed significantly increased association between the MTHFR rs1801133 polymorphism and EH risk (such as T vs. C: OR = 1.38, 95% CI = 1.25 - 1.54, P ≤ 0.001), with similar results evident within race subgroups (such as Asian: T vs. C: OR = 1.47, 95% CI = 1.30 - 1.67, P ≤ 0.001; compared to Chinese: T vs. C: OR = 1.54, 95% CI = 1.33 - 1.79, P ≤ 0.001). Similar associations were also found in subgroups defined by the source of controls and genotype methods. To our regret, based on the limited studies, no association was detected for rs1801131 polymorphism. Conclusions: Our study provides evidence that the MTHFR rs1801133 null genotype may increase EH risk. Future studies with larger sample sizes are warranted to evaluate this association in more detail.

Effect of ACE, ACE2 and CYP11B2 gene polymorphisms and noise on essential hypertension among steelworkers in China: a case-control study.

BACKGROUND: Previous studies on the relationship between ACE I/D, ACE2 G8790A and CYP11B2-344T/C gene polymorphisms and essential hypertension (EH) were inconsistent. Moreover, few studies have reported the combined effect of these gene polymorphisms and noise exposure on EH. The purpose of this study was to explore the combined and separate effects of ACE I/D, ACE2 G8790A and CYP11B2-344T/C gene polymorphisms and noise on EH among steelworkers. METHODS: A case-control study was conducted on 725 male workers between March 2014 and July 2014 in the Tangsteel Company, China. The noise exposure of the workers were measured. Logistic regression and crossover analysis were used to analyse the effects of the interactions on the EH among steelworkers. GMDR was used to determine the best combination model of gene-noise interactions. RESULTS: Multivariate logistic regression showed that noise exposure increased the odds of EH, and the OR is 1.52 (95% CI 1.04-2.22). The risk of having EH for ACE I/D DD genotype carriers was 1.99 times that for II genotype carriers (95% CI 1.14-3.51). There was a negative additive interaction between ACE2 G8790A and CYP11B2-344T/C on EH (U3 = - 2.221, P = 0.026, and S = 0.128) and a positive multiplicative interaction between ACE I/D and CYP11B2-344T/C on essential hypertension (P = 0.041). In addition, there was no significant gene-noise interaction model through the GMDR method after adjusting the confounders. CONCLUSIONS: The ACE DD genotype may make men susceptible to EH. Simultaneously carrying the DD genotype of ACE I/D and the TC genotype of CYP11B2-344T/C increased the risk of EH.

Association of lncRNA PVT1 Gene Polymorphisms with the Risk of Essential Hypertension in Chinese Population.

Vascular dysfunction and hyperlipidemia are essential risk factors contributing to essential hypertension (EH). The plasmacytoma variant translocation 1 (PVT1) is involved in modulating angiogenesis in tumor tissues and plays an important role in fat differentiation in the progress of obesity. Therefore, we selected two tagSNPs of PVT1 (rs10956390 and rs80177647) to investigate whether they are contributing to the risk of hypertension in Chinese patients. In total, 524 adult patients with EH and 439 matched healthy controls were enrolled for two central of China. Results. PVT1 rs10956390 and rs80177647 polymorphisms were genotyped by using TaqMan assay. PVT1 rs10956390 TT genotype was associated with a decreased risk of EH (OR = 0.561, 95% CI = 0.372-0.846, P = 0.006), while rs80177647 TA genotype was associated with an increased risk (OR = 2.236, 95% CI = 1.515-3.301, P < 0.001). Rs10956390 T allele was associated with lower triglyceride levels in the plasma both from healthy and EH donors. What is more, there is an association between rs10956390 polymorphism and HDL-C level, as well as LDL-C. Conclusion. PVT1 rs10956390 and rs80177647 polymorphisms may contribute to the risk of EH in Chinese population by regulating blood lipid levels.

Chromodomain Helicase DNA Binding Protein 1-like, a negative regulator of Forkhead box O3a, promotes the proliferation and migration of Angiotensin II-induced vascular smooth muscle cells.

Essential hypertension (EH) represents a major risk factor for stroke, myocardial infarction, and heart failure. Dysregulated proliferation and migration of vascular smooth muscle cells (VSMCs) play an important role in pathogenesis of EH. This study aims to investigate the effect of Chromodomain Helicase DNA Binding Protein 1-Like (CHD1L) on Angiotensin II (AngII)-induced VSMCs injury and reveal the underlying mechanism. The expression of CHD1L in EH patients was determined by bioinformatics analysis, and then it was silenced in AngII-induced VSMCs to detect the changes in cellular functions including proliferation, migration, invasion and phenotypic switching via CCK-8, EDU staining, wound healing, transwell and Western blot assays, respectively. Inflammation and oxidative stress were also measured by detecting related markers via commercial kits. After confirming the binding sites between forkhead box O3A (FOXO3a) and CHD1L and their negative association by bioinformatics analysis, FOXO3a was further silenced, and the cellular functions were assessed again to reveal the underlying mechanism. Results showed that CHD1L was highly expressed in EH, and interference of CHD1L suppressed the proliferation, migration, invasion and phenotypic switching in VSMCs. Inflammation and oxidative stress were also restrained by CHD1L knockdown. After validating the negative role of FOXO3a in regulating CHD1L, it was found that FOXO3a abrogated the effect of CHD1L knockdown on the cellular functions of AngII-induced VSMCs. In conclusion, FOXO3a suppresses the proliferation and migration of AngII-induced VSMCs by down-regulating CHD1L.

Associations between the TNMD rs4828038 and ACE2 rs879922 polymorphisms and preeclampsia susceptibility: a case-control study.

A case-control study was designed to investigate the association between the angiotensin converting enzyme 2 (ACE2) rs879922, glucose-6-phosphate dehydrogenase (G6PD) rs1050828, and tenomodulin (TNMD) rs4828038 single nucleotide polymorphisms (SNPs), and preeclampsia. A total of 356 Han Chinese pregnant women (170 controls and 186 cases) were recruited into the study. ACE2 rs879922, G6PD rs1050828, and TNMD rs4828038 were tested by the targeted next-generation sequencing technology and the data were analyzed using SPSS version 18. Genotyping of results revealed that patients with the CC/CT genotype in SNP rs4828038 or CC/CG genotype in SNP rs879922 had a significantly decreased susceptibility to late-onset preeclampsia (CC/CT versus TT: OR = 0.543, 95% CI = 0.378 to 0.779, p = .001; CC/CG versus GG: OR = 0.510, 95% CI = 0.038 to 0.860, p = .012). Our study found that the polymorphisms TNMD rs4828038 and ACE2 rs879922 might be associated with late-onset preeclampsia.IMPACT STATEMENTWhat is already known on this subject? Preeclampsia is associated with multiple SNPs, and ACE2 rs879922, G6PD rs1050828, and TNMD rs4828038 are related to essential hypertension and glucose and lipid metabolism disorders. Essential hypertension, diabetes, and dyslipidemia are risks for preeclampsia. The associations between those three SNPs and preeclampsia have not been reported.What do the results of this study add? The polymorphisms of TNMD rs4828038 and ACE2 rs879922 might be associated with the risk of late-onset preeclampsia. There was no relationship between SNP rs1050828 and preeclampsia.What are the implications of these findings for clinical practice and/or further research? TNMD rs4828038 and ACE2 rs879922 might be target sites for genetic diagnosis and therapy, and the levels of mRNA and protein in pregnant women with preeclampsia should be further tested.