Association between eNOS rs1799983 polymorphism and hypertension: a meta-analysis involving 14,185 cases and 13,407 controls.

BACKGROUND: Essential hypertension is a complex disease determined by the interaction of genetic and environmental factors, eNOS is considered to be one of the susceptible genes for hypertension. Our study aimed to evaluate the association between eNOS rs1799983 polymorphism and hypertension, and to provide evidence for the etiology of hypertension. METHODS: Case-control studies of eNOS rs1799983 polymorphism and hypertension were included by searching PubMed, Embase, Web of Science, Medline, Scopus, WanFang datebase, Vip datebase, and CNKI database according to PRISMA guideline. Eligible data were extracted and pooled, and were analyzed using R software based on five different genetic models. RESULTS: A total of 60 eligible articles involving 14,185 cases and 13,407 controls were finally selected. We found significant association between eNOS rs1799983 polymorphism and hypertension under any genetic model (T vs G: OR = 1.44, 95% CI 1.26-1.63; GT vs GG: OR 1.34, 95% CI 1.18-1.52; TT vs GG: OR 1.80, 95% CI 1.41-2.31; GT + TT vs GG: OR 1.42, 95% CI 1.25-1.63; TT vs GG + GT: OR 1.68, 95% CI 1.35-2.08; GT vs GG + TT: OR 1.24, 95% CI 1.11-1.40). CONCLUSIONS: We found that eNOS rs1799983 polymorphism is associated with the increased risk of hypertension under any genetic model. Moreover, investigations of gene-gene and gene-environment interactions are needed to give more insight into the association between eNOS rs1799983 polymorphism and hypertension.

Association between insulin resistance and left ventricular hypertrophy in asymptomatic, Black, sub-Saharan African, hypertensive patients: a case-control study.

BACKGROUND: Conflicting information exists regarding the association between insulin resistance (IR) and left ventricular hypertrophy (LVH). We described the associations between obesity, fasting insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), and LVH in Black patients with essential hypertension. METHODS: A case-control study was conducted at the Centre Médical de Kinshasa (CMK), the Democratic Republic of the Congo, between January and December 2019. Cases and controls were hypertensive patients with and without LVH, respectively. The relationships between obesity indices, physical inactivity, glucose metabolism and lipid disorder parameters, and LVH were assessed using linear and logistic regression analyses in simple and univariate exploratory analyses, respectively. When differences were observed between LVH and independent variables, the effects of potential confounders were studied through the use of multiple linear regression and in conditional logistic regression in multivariate analyses. The coefficients of determination (R2), adjusted odds ratios (aORs), and their 95% confidence intervals (95% CIs) were calculated to determine associations between LVH and the independent variables. RESULTS: Eighty-eight LVH cases (52 men) were compared against 132 controls (81 men). Variation in left ventricular mass (LVM) could be predicted by the following variables: age (19%), duration of hypertension (31.3%), body mass index (BMI, 44.4%), waist circumference (WC, 42.5%), glycemia (20%), insulinemia (44.8%), and HOMA-IR (43.7%). Hypertension duration, BMI, insulinemia, and HOMA-IR explained 68.3% of LVM variability in the multiple linear regression analysis. In the logistic regression model, obesity increased the risk of LVH by threefold [aOR 2.8; 95% CI (1.06-7.4); p = 0.038], and IR increased the risk of LVH by eightfold [aOR 8.4; 95 (3.7-15.7); p < 0.001]. CONCLUSION: Obesity and IR appear to be the primary predictors of LVH in Black sub-Saharan African hypertensive patients. The comprehensive management of cardiovascular risk factors should be emphasized, with particular attention paid to obesity and IR. A prospective population-based study of Black sub-Saharan individuals that includes the use of serial imaging remains essential to better understand subclinical LV deterioration over time and to confirm the role played by IR in Black sub-Saharan individuals with hypertension.

Association between the A46G polymorphism (rs1042713) in the ß2-adrenergic receptor gene and essential hypertension susceptibility in the Chinese population: A PRISMA-compliant meta-analysis.

BACKGROUND: Recently, many studies have been conducted to investigate the relationship between the A46G polymorphism in the ß2-adrenergic receptor (ADRB2) gene and essential hypertension risk in the Chinese population. However, the results of previous studies were conflicting. OBJECTIVES: The present study aimed to investigate the association between the ADRB2 A46G polymorphism and the risk of essential hypertension in the Chinese population. METHODS: We performed a systematic search of possible relevant studies on PubMed, Embase, Ovid, Web of Science, China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc databases up to January 3, 2020. Two authors independently extracted information from included articles and assessed the quality of each study by the use of the Newcastle-Ottawa Scale. According to the extent of interstudy heterogeneity, either a random-effect model or a fixed-effect model was used to calculate the combined odds ratio (OR) and 95% confidence interval (CI). RESULTS: Finally, 16 studies containing 3390 cases and 2528 controls were included in our meta-analysis. Significant associations were found between the ADRB2 A46G polymorphism and essential hypertension risk in the Chinese population under four genetic models: allele genetic model (OR: 1.14, 95% CI: 1.06-1.23, P = .001, Pheterogeneity = .09), homozygote genetic model (OR: 1.29, 95% CI: 1.11-1.51, P = .001, Pheterogeneity = .25), dominant genetic model (OR: 1.17, 95% CI: 1.05-1.32, P = .005, Pheterogeneity = .04), and recessive genetic model (OR: 1.21, 95% CI: 1.05-1.38, P = .007, Pheterogeneity = .72). CONCLUSION: The ADRB2 A46G polymorphism may increase the risk of essential hypertension in the Chinese population.

Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure.

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P<1×10-5. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (P<1×10-7) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P<0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 (TXNIP) and cg00716257 (JDP2) determined by environmental effects acting on both systolic BP and methylation levels.

Genetic forms and pathophysiology of essential arterial hypertension in minor indigenous peoples of Russia.

BACKGROUND: To study the genetic forms and pathophysiology of arterial hypertension by evaluating plasma renin activity in the Shors, minor indigenous peoples inhabiting the south of Western Siberia. METHODS: A single-stage study of indigenous (the Shors) and non-indigenous peoples living in the villages of Gornaya Shoria of the Kemerovo region in the south of Western Siberia was conducted in the period from 2013 to 2017. One thousand four hundred nine adults (901 Shors and 508 non-indigenous inhabitants) were recruited in the study using a continuous sampling plan. Arterial blood pressure was measured according to 2018 ESC/ESH guidelines for the management of arterial hypertension. All the respondents underwent clinical and instrumental examination. Plasma renin activity was determined by enzyme-linked immunoassay with the BRG kits (Germany). Polymorphisms of ACE (I/D, rs 4340), АGT (c.803 T > C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A > G, Ser49Gly, rs1801252) and ADRA2B (I/D, rs 28,365,031) genes were tested using polymerase chain reaction. RESULTS: Renin-dependent hypertensive patients prevailed in both ethnic groups (65.6% in the indigenous group vs. 89.8% in the non-indigenous group, p = 0.001). Prevalence of a volume-dependent AH was low in both groups (34.4% in the indigenous group vs. 10.2% in the non-indigenous group, р = 0.001). The D/D and Т/Т genotypes of the АСЕ [OR = 6.97; 95% CI (1.07-55.58)] and AGT [OR = 3.53; 95% CI (1.02-12.91)] genes were associated with the renin-dependent AH in the Shors. The C/C genotype of AGTR1 gene was found to predispose to the volume-dependent AH [OR = 5.25; 95% CI (1.03-27.89)]. The C/C genotype of AGTR1 gene was associated with moderate or high renin levels suggesting essential AH in the non-indigenous group [OR = 5.00; 95% CI (1.21-22.30), р = 0.029]. CONCLUSION: An in-depth understanding of AH pathophysiology and its genetic forms ensures the optimal choice of blood pressure-lowering treatment and optimizes AH control.

KLHL3 single-nucleotide polymorphism is associated with essential hypertension in Chinese Han population.

Hypertension, including secondary and essential hypertension (EH) variants, is a multifactorial disease, affecting more than one billion people worldwide. Secondary hypertension results from mutations in the putative gene KLHL3 (Kelch-like protein 3); however, it has not been reported whether the KLHL3 gene polymorphisms are associated with EH. Here, we investigated the association between KLHL3 (rs2301708 and rs7444370) polymorphisms and EH in the Chinese Han population.This case-control study included 522 subjects-260 patients with EH and 262 normotensive controls matched for age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and levels of Na, K, and Cl. The distribution of functional rs2301708 and rs7444370 polymorphisms within the KLHL3 gene was assessed through polymerase chain reaction (PCR) and restriction-fragment length polymorphism (RFLP).There was no significant difference in allelic and genotypic frequencies of KLHL3 rs2301708 between the EH and normotensive groups; however, the rs7444370 T allele and CT genotype in females was significantly associated with a protective effect against EH (P = .001, P = .002; P = .019, P = .052), and the haplotype CT of rs2301708 and rs7444370 among females in the EH group was less than in the normotensive group (P = .000; P = .007).The KLHL3 rs7444370 variant could be a protective factor in the pathogenesis of females' EH.

Screening of differentially expressed microRNAs of essential hypertension in Uyghur population.

BACKGROUND: Essential hypertension can cause many kinds of cardiovascular diseases. The pathogenesis of essential hypertension is very complex, and the mechanism is still unclear. The microRNAs have been identified as novel biomarkers for pre-diagnosis and prognosis of hypertension. However, the kinds of microRNAs that can be used as specific biomarkers for hypertension are unknown. METHODS AND RESULTS: Plasma samples were isolated from Uyghur subjects with essential hypertension and the healthy individuals. Microarray was used to identify differentially expressed microRNAs. The microarray data were clustered and annotated with online software. The target genes of differentially expressed microRNAs were also analyzed. The microarray results were further verified by quantitative real-time PCR. We identified 257 microRNAs that were differentially expressed between patients with essential hypertension and the healthy individuals. These microRNAs had a total of 6580 target genes. The 47 microRNAs that had target genes, including 24 up-regulated and 23 down-regulated microRNAs, were further screened out to construct a reference set of potential microRNA biomarkers. Most of the 47 microRNAs were located at chromosome 19 (40 microRNAs) and chromosome 1 (45 microRNAs). Their target genes were mainly enriched in metal ion binding, transcription regulation, cell adhesion and junction, indicating that these candidate microRNAs may regulate mineral ion binding and cell communication process of essential hypertension. The quantitative real-time PCR results of miR-198 and miR-1183 (which were the two most significantly up-regulated microRNAs by microarray), and, miR-30e-5p and miR-144-3p (which were the two most significantly down-regulated microRNAs by microarray) were consistent with the microarray results. CONCLUSIONS: A reference set of potential microRNA biomarkers that may be involved in essential hypertension is constructed. Our study may provide experimental evidence for further studying the mechanism of essential hypertension.

Plasma Renin Activity Is a Predictive Biomarker of Blood Pressure Response in European but not in African Americans With Uncomplicated Hypertension.

BACKGROUND: Interindividual variability in blood pressure (BP) response to antihypertensives has been reported. Although plasma renin activity (PRA) is a potential biomarker for personalizing antihypertensive therapy in European American (EA) and African American (AA) hypertensives, clinical utility of PRA-guided prescribing is incompletely understood. METHODS: Using systematic-phased approach, PRA's clinical utility was assessed. After categorizing by baseline PRA, clinic systolic BP (SBP) responses to metoprolol and chlorthalidone were compared in 134 EAs and 102 AAs enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses-2 (PEAR-2) trial. Receiver operating characteristic (ROC) analysis was conducted in EAs. Data from PEAR-2 AAs were used to estimate an optimal PRA cut point using multivariable linear regression models. The derived cut point in AAs was tested in a meta-analysis of 2 independent AA cohorts, and its sensitivity and specificity were assessed. RESULTS: EAs with PRA < 0.65 ng/ml/hour had a greater decrease in SBP to chlorthalidone than metoprolol (by -15.9 mm Hg, adjusted P < 0.0001), whereas those with PRA ≥ 0.65 ng/ml/hour had a greater decrease in SBP to metoprolol than chlorthalidone (by 3.3 mm Hg, adjusted P = 0.04). Area under ROC curve (0.69, P = 0.0001) showed that PRA can predict SBP response among EAs. However, we observed no association between PRA and SBP response in PEAR-2 AAs. Among independent AA cohorts, those with PRA ≥ 1.3 ng/ml/hour (PEAR-2-derived cut point) responded better to atenolol/candesartan than hydrochlorothiazide (meta-analysis P = 0.01). However, sensitivity of the derived cut point was 10%. CONCLUSIONS: PRA at the previously established 0.60-0.65 ng/ml/hour cut point is an effective predictive biomarker of BP response in EAs. However, we were unable to identify PRA cut point that could be used to guide antihypertensive selection in AAs. TRIAL REGISTRATION: NCT01203852, NCT00246519, NCT00005520.

A comprehensive meta-analysis on relationship between CYP11B2 rs1799998 polymorphism and atrial fibrillation.

BACKGROUND: The correlation between CYP11B2 rs1799998 polymorphism and atrial fibrillation (AF) was analyzed by several studies, but the results of these studies were inconsistent. Thus, we performed this study to obtain a more conclusive result on relationship between CYP11B2 rs1799998 polymorphism and AF. METHODS: Eligible studies were searched in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of correlation. RESULTS: A total of 12 studies with 5466 participants were analyzed. We found that CYP11B2 rs1799998 polymorphism was significantly associated with AF in overall population under recessive genetic model with FEM (P = 0.005, OR = 1.29, 95%CI 1.08-1.54), but no positive results were detected in overall analyses with REMs. Further subgroup analyses revealed that CYP11B2 rs1799998 polymorphism was significantly correlated with AF in East Asians, but not in West Asians. Furthermore, significant associations between rs1799998 polymorphism and AF were observed in subjects with essential hypertension (EH) and heart failure (HF). No any other positive results were found in overall and subgroup analyses. CONCLUSIONS: Overall, our meta-analysis suggested that rs1799998 polymorphism may serve as a potential biological marker of AF in East Asians and subjects with EH or HF.

Association of uncoupling protein gene polymorphisms with essential hypertension in a northeastern Han Chinese population.

Uncoupling proteins (UCPs) belong to the family of mitochondrial transporter proteins and mediate regulated proton leak across the inner mitochondrial membrane. The UCPs play an important role in energy homeostasis and reactive oxygen species (ROS) release, and have been established as candidate genes for obesity, diabetes and hypertension. This study examined the possible association between the single nucleotide polymorphisms (SNPs) of UCP1-3 genes and essential hypertension (EH) in a northeastern Han Chinese population. A total of 2207 Chinese Han subjects were enrolled, including 1045 normotensives and 1162 hypertensives. Genotyping of UCP1 rs1800592, UCP1 rs12502572, UCP2 rs659366, UCP2 rs660339, and UCP3 rs3781907 was detected using Sequenom MassArray System. SHEsis was used to analyze linkage disequilibrium and haplotype. No evident association was observed between the genotype distributions and allele frequencies of individual SNPs and EH. Haplotype analysis showed the haplotype GAATA (rs1800592-rs12502572-rs659366-rs660339-rs3781907) was significantly associated with lower EH risk (p = 0.001, χ2 = 10.861, OR = 0.634, 95% CI = 0.483-0.833), and AGATG was associated with increased EH risk (p = 0.012, χ2 = 6.287, OR = 1.265, 95% CI = 1.052-1.521). These findings suggest haplotypes of UCP1-3 genes are linked to EH risk in a northeastern Han Chinese population. Further investigation with larger sample size in multiethnic population is needed to confirm our results.

Efficacy and safety of azilsartan medoxomil/chlortalidone fixed-dose combination in hypertensive patients uncontrolled on azilsartan medoxomil alone: A randomized trial.

Patients with grade 2-3 essential hypertension and postplacebo mean clinic systolic blood pressure (SBP) 160-190 mm Hg and 24-hour SBP 140-175 mm Hg by ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil (AZL-M) monotherapy for 4 weeks. "Nonresponders" were then randomized to 8 weeks of double-blind treatment with AZL-M 40 mg, AZL-M/chlortalidone (CLD) 40/25, or AZL-M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was -21.1 (±1.04) mm Hg for AZL-M/CLD 40/25 mg, -15.8 (±1.08) mm Hg for AZL-M/CLD 40/12.5 mg, and -6.4 (±1.05) mm Hg for AZL-M 40 mg (P < 0.001 for both AZL-M/CLD vs AZL-M, ANCOVA). Drug discontinuation rates were 8.9% (AZL-M/CLD 40/25 mg), 7.5% (AZL-M 40 mg), and 3.9% (AZL-M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL-M/CLD 40/25), 3.1% (AZL-M/CLD 40/12.5 mg), and 3.0% (AZL-M 40 mg) of patients. AZL-M/CLD was effective and well tolerated in patients not achieving blood pressure targets with AZL-M.

Unexpected role of the human cytomegalovirus contribute to essential hypertension in the Kazakh Chinese population of Xinjiang.

Human cytomegalovirus (HCMV) infection, chronic inflammation and oxidative stress, the renin-angiotensin system (RAS), endothelial function, and DNA methylation play roles in the pathogenesis of essential hypertension (EH); however, the mechanism by which HCMV predisposes patients to hypertension remain unclear. Our group previously demonstrated an association between EH and HCMV infection in Kazakh Chinese. Here, we investigated the relationship between HCMV infection and other clinicopathological features in 720 Kazakh individuals with or without hypertension (n=360 each; age: 18-80). Multiple linear and logistic regression analyses were used to determine the associations between HCMV infection, clinical characteristics, and EH. Notably, patients with EH, particularly those with HCMV infection, exhibited a marked increase in tumor necrosis factor-α (TNF-α) and 8-hydroxy-2-deoxyguanosine (8-OHDG) levels, but a decrease in endothelial nitric oxide synthase (eNOS) and renin levels. Similarly, elevated TNF-α and 8-OHDG levels were independent predictors of increased HCMV antibody titers, whereas eNOS and renin were negatively correlated with the latter. Moreover, serum angiotensin-converting enzyme (sACE, ACE) methylation was increased, whereas 11-ß hydroxysteroid dehydrogenase 2 (HSD11ß2; HSD3B2) methylation was decreased in patients with EH who were also infected with HCMV. A positive correlation between HSD3B2 methylation and HCMV IgG titer and blood pressure was additionally observed, whereas angiotensin-converting enzyme (ACE) methylation was inversely correlated with blood pressure. Collectively, these data indicate that HCMV may contribute to EH development in the Kazakh Chinese by increasing TNF-α and 8-OHDG levels, suppressing eNOS and renin, and manipulating HSD3B2 and ACE methylation.

Common variant rs11191548 near the CYP17A1 gene is associated with hypertension and the serum 25(OH) D levels in Han Chinese.

The CYP17A1 gene, which encodes17α-hydroxylase and 17,20-lyase, has been identified as a common hypertension susceptibility locus in a European population. However, the association between CYP17A1 polymorphisms and hypertension is unclear in the Chinese population as well as in the role of serum 25(OH) D levels. Six single nucleotide polymorphisms (SNPs) in CYP17A1 were genotyped in two stages in a Han Chinese population, and the serum 25(OH) D levels were measured. Analysis in stage 1 showed that the rs1004467 minor G-allele and rs11191548 minor C-allele in CYP17A1 were significantly associated with a decreased risk of hypertension and higher serum 25(OH) D levels (all P < 0.05). The larger sample in stage 2 also showed that a mutation in rs11191548 was significantly associated with a decreased risk of hypertension (adjusted OR = 0.707, 95% CI: 0.553-0.904, P = 0.006). The rs11191548 minor C-allele was associated with higher serum 25(OH) D levels in hypertensive subjects (ßadj ± SEM = 0.094 ± 0.949, P = 0.003) and controls (ßadj ± SEM = 0.128 ± 1.025, P < 0.001). In conclusion, the rs11191548 CYP17A1 gene mutation was associated with hypertension and the serum 25(OH) D levels in Han Chinese.

Genome Wide Association Study Identifies the HMGCS2 Locus to be Associated With Chlorthalidone Induced Glucose Increase in Hypertensive Patients.

BACKGROUND: Thiazide and thiazide-like diuretics are first-line medications for treating uncomplicated hypertension. However, their use has been associated with adverse metabolic events, including hyperglycemia and incident diabetes mellitus, with incompletely understood mechanisms. Our goal was to identify genomic variants associated with thiazide-like diuretic/chlorthalidone-induced glucose change. METHODS AND RESULTS: Genome-wide analysis of glucose change after treatment with chlorthalidone was performed by race among the white (n=175) and black (n=135) participants from the PEAR-2 (Pharmacogenomic Evaluation of Antihypertensive Responses-2). Single-nucleotide polymorphisms with P<5×10-8 were further prioritized using in silico analysis based on their expression quantitative trait loci function. Among blacks, an intronic single-nucleotide polymorphism (rs9943291) in the HMGCS2 was associated with increase in glucose levels following chlorthalidone treatment (ß=12.5; P=4.17×10-8). G-allele carriers of HMGCS2 had higher glucose levels (glucose change=+16.29 mg/dL) post chlorthalidone treatment compared with noncarriers of G allele (glucose change=+2.80 mg/dL). This association was successfully replicated in an independent replication cohort of hydrochlorothiazide-treated participants from the PEAR study (ß=5.54; P=0.023). A meta-analysis of the 2 studies was performed by race in Meta-Analysis Helper, where this single-nucleotide polymorphism, rs9943291, was genome-wide significant with a meta-analysis P value of 3.71×10-8. HMGCS2, a part of the HMG-CoA synthase family, is important for ketogenesis and cholesterol synthesis pathways that are essential in glucose homeostasis. CONCLUSIONS: These results suggest that HMGCS2 is a promising candidate gene involved in chlorthalidone and Hydrochlorothiazide (HCTZ)-induced glucose change. This may provide insights into the mechanisms involved in thiazide-induced hyperglycemia that may ultimately facilitate personalized approaches to antihypertensive selection for hypertension treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00246519 and NCT01203852.

[Association of sodium ion transporter gene polymorphisms with essential hypertension among ethnic Koreans from Mudanjiang].

OBJECTIVE To assess the association of SLC12A3 and SCNN1B gene polymorphisms (rs11643718 and rs12447134) with essential hypertension among ethnic Koreans from Mudanjiang, China. METHODS For 204 patients with essential hypertension and 186 healthy controls, the genotypes of rs11643718 and rs12447134 loci were determined with an improved multiplex ligase detection reaction (iMLDR) method. RESULTS Allelic and genotypic frequencies of rs11643718 of SLC12A3 gene are associated with the onset of disease hypertension (P <0.05) as well as systolic blood pressure (P < 0.01, under a recessive model). No association was found between rs12447134 of SCNN1B gene with the onset of disease (P > 0.05) but diastolic blood pressure (P < 0.05, under a recessive model). CONCLUSION The polymorphisms of rs11643718 locus is associated with the susceptibility for essential hypertension among ethnic Koreans from Mudanjiang area and can be used as a predictor for the disease.

Evaluation of the Saline Infusion Test and the Captopril Challenge Test in Chinese Patients With Primary Aldosteronism.

Context: The aim of this study was to determine whether the diagnosis cutoff values associated with the saline infusion test (SIT) and captopril challenge test (CCT) in the Endocrine Society guidelines are applicable to Chinese subjects. Objective and Design: We performed a head-to-head comparison of the SIT and CCT among Chinese subjects with primary aldosteronism (PA) and essential hypertension (EH). Participants and Setting: One hundred sixty-four hypertensive patients were enrolled. Intervention: All participants underwent both the SIT and CCT. Main Outcome Measures: The plasma aldosterone concentration (PAC) and plasma renin activity were measured before and after the SIT and CCT. The degree of PAC decline after CCT was calculated. Results: This study included 115 PA and 49 EH subjects. The prevalence of hypokalemia was 74.8% in the PA group. Supine PACs in the EH and PA groups were 15.1 ± 4.7 mmol/L and 30.4 ± 12.1 mmol/L. Post-SIT PACs were 8.8 ± 1.7 ng/dL and 22.7 ± 10.2 ng/dL in the EH and PA groups. The degree of PAC decline after CCT was 17.7% and 14.2% in the EH and PA groups; post-CCT PACs were 11.7 ± 3.3 ng/dL and 25.9 ± 10.6 ng/dL. PAC values of 11.2 ng/dL and 16.7 ng/dL after the SIT and CCT represented the optimal cutoff values for PA diagnosis. The post-SIT and post-CCT area under the receiver operating characteristic curve values were 0.972 [95% confidence interval (CI) = 0.934 to 0.991] and 0.933 (95% CI = 0.883 to 0.966). Conclusions: Post-SIT and post-CCT PACs, but not the degree of PAC suppression, were both reliable for PA diagnosis. However, the optimal cutoffs were slightly higher in Chinese subjects than those recommended by the Endocrine Society.

Replication of a genome-wide association study on essential hypertension in Mongolians.

Replication of genome-wide significant association SNPs in independent populations is an essential approach for identifying gene-disease relationships. Therefore, we sought to investigate the top 21 SNPs (rs10507454, rs11897156, rs11897991, rs12325203, rs12541835, rs13395322, rs1525035, rs16936892, rs17010027, rs17045859, rs17136827, rs1866525, rs2045590, rs4547758, rs4655688, rs7107438, rs761353, rs8127139, rs9312305, rs9407874 and rs9865108) from a genome-wide association study of essential hypertension in Mongolians. This was a community-based case-control study involving 428 hypertensives and 638 normotensives from Kerqinzuoyihou Banner,Tongliao, Inner Mongolian Autonomous Region, China. Genotyping was conducted with Sequenom MassArray (®) SNP detection technology. Overall, there were no significant differences in the genotype distributions and allele frequencies between the cases and controls. There was a significant difference between the allele frequencies at locus rs17010027 in cases (high systolic blood pressure) and controls in female (p = .036). There were significant differences in the distribution of genotypes and the allele frequencies at locus rs10507454 between cases (high diastolic blood pressure) and controls (p = .019 and p = .022, respectively) especially in male (p = .009 and p = .011, respectively). rs17010027 is associated with high systolic blood pressure in female, and rs10507454 is associated with high diastolic blood pressure especially in male of this Mongolian population.

Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute Salt Loading.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) increases the risk of cardiovascular complications, and the heritability of SSBP is about 50% in Chinese population. However, studies identifying genes involved in BP responses to acute sodium loading and diuresis shrinkage are still limited. METHOD: A total of 342 essential hypertensives from Beijing were recruited in our study. A modified Sullivan's acute oral saline load and diuresis shrinkage test was conducted to each individual. Medical history and lifestyle risk factors were obtained by questionnaire. Generalized linear model was used to examine the associations of 29 single-nucleotide polymorphisms (SNPs) with SSBP and false discovery rate (FDR) was used to correct P values for multiple testing. RESULTS: In the process of acute sodium loading, after adjusting for age and 24-hour urinary sodium concentration, SNPs in CYP11B2, PRKG1, SLC8A1 genes were significantly associated with systolic BP (SBP) rising in the additive and recessive model; SNPs in CYP4A11, PRKG1, SLC8A1, and ADRB2 genes were significantly associated with diastolic BP (DBP) rising. In the process of diuresis shrinkage, SNPs of CLCNKA, eNOS, PRKG1 gene were associated with SBP and DBP decreasing. After FDR correction, rs434082 in SLC8A1 gene was still significantly associated with blood pressure rising during salt load. In the additive model, A allele increased DBP of 2.8 mm Hg (FDR_q = 0.029) and MAP of 3.1 mm Hg (FDR_q = 0.029) after adjusting for age and 24-hour urinary sodium concentration. CONCLUSION: SLC8A1 gene may contribute to BP change in the process of acute sodium loading in a Han Chinese population.

Association of G-protein ß3 subunit C825T polymorphism with essential hypertension: evidence from 63 729 subjects.

Many studies have reported that G-protein ß3 subunit (GNB3) C825T polymorphism is associated with essential hypertension (EH), although this remains subject to debate. Thus, meta-analysis was carried out to clarify this relationship. A total of 75 articles, reporting 81 case-control studies evaluating 28 369 patients and 34 933 control individuals, were assessed. Overall, a significant association was observed in the dominant model (odds ratio (OR)=1.11, 95% CI 1.04-1.19), recessive model (OR=1.09, 95% CI 1.01-1.17), TT vs CC (OR=1.16, 95% CI 1.05-1.28), CT vs CC (OR=1.09, 95% CI 1.02-1.17), and additive model (OR=1.07, 95% CI 1.02-1.13) after pooling all eligible studies. Subgroup analysis by ethnicity and gender demonstrated significantly increased EH only in Caucasians using the dominant (OR=1.22, 95% CI 1.07-1.39; TT vs CC, OR=1.29, 95% CI 1.07-1.54; CT vs CC, OR=1.19, 95% CI 1.05-1.35) and additive (OR=1.16, 95% CI 1.05-1.28) models. In summary, the present meta-analysis indicated the GNB3 C825T polymorphism is related to increased EH exclusively in Caucasians.

[Effects of angiotensin-converting enzyme gene and environment interaction on essential hypertension in the Han nationality].

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme( ACE) gene I/D and A2350 G polymorphisms with environmental factors interaction on essential hypertension in the Han nationality. METHODS: A population-based case-control study was conducted, and 1010 patients with hypertension and 1030 normal controls were recruited from Lanxi Country rural, Heilongjiang Province. ACE gene two polymorphism sites were detected by polymerase chain reaction-restriction fragment length polymorphism( PCR-RFLP). Using multivariate Logistic regression to analysis the interaction between gene polymorphisms and environmental factors. RESULTS: The distributions of ACE two polymorphism sites genotypes in control group were in accordance with the HardyWeinberg equilibrium( HWE). Multivariate Logistic analysis showed that age, gender, family history of hypertension, BMI, TG and high-density lipoprotein enter the model and were the risk factors for essential hypertension( P < 0. 05), especially, family history of hypertension( χ~2= 53. 488, OR = 2. 140, 95% CI 1. 746-2. 625). The interaction analysis between two sites genotype and environmental factors, noted that there were statistically significant combination effect between genotypes of the two sites and the factors of age, gender, BMI, TG and high-density lipoprotein. There was multiplication interaction only between I/D and age( P = 0. 0356, OR = 1. 021, 95% CI 1. 001-1. 021). CONCLUSION: There are combination effect between ACE gene I/D and A2350 G polymorphisms with multiple environmental factors, which are likely to increase the risk of suffering from essential hypertension.