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.

C1q/TNF-related protein-9 is elevated in hypertension and associated with the occurrence of hypertension-related atherogenesis.

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

Association of ECE1 gene polymorphisms and essential hypertension risk in the Northern Han Chinese: A case-control study.

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

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

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

Expression Profile of microRNAs in Hypertrophic Cardiomyopathy and Effects of microRNA-20 in Inducing Cardiomyocyte Hypertrophy Through Regulating Gene MFN2.

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

Single Nucleotide Polymorphisms (SNPs) Genotyping Reveals that Mfn2 Polymorphisms are Associated with Thoracic Aortic Dissection in Han Chinese Population.

BACKGROUND Many studies have shown that hypertension may contribute to thoracic aortic dissection (TAD). Among the factors that modulate hypertension are endoplasmic reticulum stress and vascular smooth muscle cell proliferation which are in turn modulated by mitofusion-2 (Mfn2). Specifically, we determined, in the Han Chinese population, whether single nucleotide polymorphisms (SNPs) of Mfn2 influenced the occurrence of TAD. MATERIAL AND METHODS Six tagging SNPs of Mfn2 (rs2236057, rs3766741, rs2236058, rs17037564, rs2295281, and rs2336384) were genotyped using a TaqMan assay in 200 TAD patients and 451 health individuals from the Han Chinese population. RESULTS Logistic regression analysis indicated CC genotype of rs2295281 was highly linked to an increased risk of TAD (TT+CT versus CC, OR=0.540, 95% CI [0.320-0.911], P=0.021), implying that TT genotype and CT genotype of rs2295281 have a lower risk for TAD. Logistic regression analysis also indicated that rs2236058 was highly linked to the risk of TAD based on recessive genetic model, which indicated that the GG genotype was a protective factor against TAD (GG versus (CG+CC), OR=0.545, 95% CI [0.351-0.845], P=0.007). CG genotype and CC genotype of rs2236058 had a higher risk for TAD. In addition, rs2236058 was linked to the risk of TAD in the recessive genetic and homozygous models in the normotensive subgroup (GG versus (CG+CC), OR=0.298, 95% CI [0.112-0.792], P=0.015; GG versus CC, OR=0.528, 95% CI [0.302-0.925], P=0.026) but not in the hypertension subgroup. CONCLUSIONS Our findings showed that the occurrence of TAD in a Han Chinese population was influenced by Mfn2 polymorphisms.

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

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

Risk-Predicting Model for Incident of Essential Hypertension Based on Environmental and Genetic Factors with Support Vector Machine.

Essential hypertension (EH) has become a major chronic disease around the world. To build a risk-predicting model for EH can help to interpose people's lifestyle and dietary habit to decrease the risk of getting EH. In this study, we constructed a EH risk-predicting model considering both environmental and genetic factors with support vector machine (SVM). The data were collected through Epidemiological investigation questionnaire from Beijing Chinese Han population. After data cleaning, we finally selected 9 environmental factors and 12 genetic factors to construct the predicting model based on 1200 samples, including 559 essential hypertension patients and 641 controls. Using radial basis kernel function, predictive accuracy via SVM with function with only environmental factor and only genetic factor were 72.8 and 54.4%, respectively; after considering both environmental and genetic factor the accuracy improved to 76.3%. Using the model via SVM with Laplacian function, the accuracy with only environmental factor and only genetic factor were 76.9 and 57.7%, respectively; after combining environmental and genetic factor, the accuracy improved to 80.1%. The predictive accuracy of SVM model constructed based on Laplacian function was higher than radial basis kernel function, as well as sensitivity and specificity, which were 63.3 and 86.7%, respectively. In conclusion, the model based on SVM with Laplacian kernel function had better performance in predicting risk of hypertension. And SVM model considering both environmental and genetic factors had better performance than the model with environmental or genetic factors only.

Recent development of risk-prediction models for incident hypertension: An updated systematic review.

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

Association of the -344T/C polymorphism in aldosterone synthase gene promoter with left ventricular structure in Chinese Han: A meta-analysis.

No consensus view has been published on the relationship between the aldosterone synthase gene (CYP11B2) -344C/T polymorphism and left ventricular hypertrophy (LVH) in Chinese Han. We undertook a meta-analysis to investigate the potential association of this polymorphism and left ventricular structure-related phenotypes, including left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular end systolic diameter (LVESD), left ventricular end diastolic dimension (LVEDD), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS). Studies in English and Chinese were found based on a systematic search of Medline, Embase, CNKI, and Wanfang databases. The dominant model (TT vs. TC+CC) and homozygote model (TT vs. CC) were selected to examine the association between the -344C/T polymorphism and LVH. The random-effects model was used to pool data. From a total of 3104 participants, despite the investigation of six echocardiographic indicators, we found no significant association between the -344C/T variant and LVH in the whole group and the subgroup analyses by blood pressure. However, in the subgroup of northern Han Chinese, TT genotype had higher LVPWT than CC genotype and TC genotype (pheterogeneity = 0.4, pvalue = 0.04, 95% CI 0.09 (0.00, 0.18)). In addition, no evidence of publication bias was observed. In conclusion, our meta-analysis indicated that subjects with TT genotype might have higher risk of developing LVH in northern Han Chinese.

ADRB2 polymorphisms and dyslipidemia risk in Chinese hypertensive patients.

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

Second-generation versus first-generation drug-eluting stents in saphenous vein graftdisease: A meta-analysis of randomized controlled trials.

BACKGROUND: Second-generation drug-eluting stents (DESs) have become increasingly popular devices for patients with saphenous vein graft (SVG) disease. Second-generation DESs were designed to have more safety and efficacy than first-generation DES, but clinical outcomes in SVG disease remain conflicting. METHODS AND RESULTS: Randomized controlled trials (RCTs) were identified when comparing second- versus first-generation DESs in SVG disease. The main endpoint was all-cause death. The time of follow-up was at least 30days. The secondary endpoints were major adverse cardiovascular events (MACEs), target vessel revascularization (TVR), target lesion revascularization (TLR), myocardial infarction (MI), and stent thrombosis. These endpoints were assessed at 30days, 12months and 24months. Four RCTs with 1077 SVG patients undergoing the implantation of DES were collected in the current meta-analysis. As a result, second-generation DES-treated patients had the significantly lower MACE rates at 12months (P=0.03; OR: 0.69, 95% CI: 0.49,0.97). No differences in two groups were seen in all-cause death, MI, TVR, stent thrombosis and TLR. CONCLUSIONS: Our limited evidence indicated that, second-generation DES in SVG patients, compared with first-generation DES, offered similar levels of safety, but were more effective than the former one.

The Association of Mitofusion-2 Gene Polymorphisms with Susceptibility of Essential Hypertension in Northern Han Chinese Population.

BACKGROUND: Mitofusion-2 (Mfn2) played an important role in regulating vascular smooth muscle cells proliferation, insulin resistance and endoplasmic reticulum stress, which were found to be involved in the development of hypertension. So we inferred that the Mfn2 gene may participate in the pathogenesis of hypertension. The aim of this study was to determine whether common single nucleotide polymorphisms (SNPs) in Mfn2 gene were associated with essential hypertension (EH) in northern Han Chinese. METHODS: We genotyped 6 tagging SNPs of Mfn2 gene (rs2336384, rs2295281, rs17037564, rs2236057, rs2236058 and rs3766741) with the TaqMan assay in 626 hypertensive patients and 618 controls. RESULTS: Logistic regression analysis indicated that CC+CA genotype of rs2336384 and AA+AG genotype of rs2236057 were significantly associated with increased risk of EH (OR=1.617, P=0.005; OR=1.418, P=0.031, respectively). GG genotype of rs2236058 and GG+CG genotype of rs3766741 were found to be significantly associated with decreased risk of EH (OR=0.662, P=0.023; OR=0.639, P=0.024).When stratified by gender, for rs2336384, rs2236057 and rs2236058, significant association was observed in males, but not in females. Haplotype analysis indicated that the CCAACC haplotype was positively correlated with EH and there was a negative correlation between ACAGGG haplotype and EH. CONCLUSIONS: This study demonstrated that Mfn2 gene polymorphisms were associated with essential hypertension in northern Han Chinese population, especially in male subjects.

Association of the bradykinin receptors genes variants with hypertension: a case-control study and meta-analysis.

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

Comparing Direct Stenting With Conventional Stenting in Patients With Acute Coronary Syndromes: A Meta-Analysis of 12 Clinical Trials.

Our aim was to compare direct stenting (DS) with conventional stenting (CS) in patients with acute coronary syndrome (ACS). We searched PubMed, EMBASE, and ISI web of science for eligible studies. Primary end point was major adverse cardiac events (MACEs) in short term. Secondary end points were 1-year mortality and after-procedural no-reflow phenomenon. Twelve trials in 8998 patients were included. The odds ratios (ORs) were pooled using the Mantel-Haenszel fixed effect model. Short-term MACEs were significantly reduced in the DS arm in contrast to the CS (5.00% vs 8.08%, DS vs CS, respectively, OR [95% confidence interval] = 0.61 [0.46-0.80], P = .0004). One-year mortality and after-procedural no-reflow phenomenon were significantly lower in the DS group. No heterogeneity was observed through I(2) test (Phet = .81, .89, and .77 for each end point, respectively). This meta-analysis demonstrated that in selected patients with ACS, DS is not only safe and feasible but also reduces short-term and 1-year mortality as well as the occurrence of after-procedural no-reflow phenomenon.

Renal Denervation vs Pharmacotherapy for Resistant Hypertension: A Meta-Analysis.

The effect of renal denervation (RD) for resistant hypertension remains controversial because of the conflicting results of finished and ongoing studies. The authors performed a meta-analysis of case-control studies to identify whether renal sympathetic denervation or pharmacotherapy (PHAR) was more effective for resistant hypertension. A systematic Internet database search of relevant papers written in English was performed. A total of nine studies met the inclusion criteria, with a total of 1096 patients. When comparing the RD group with the PHAR group, there was a significant decrease in systolic blood pressure (SBP) (weighted mean difference, -12.81 mm Hg; 95% confidence interval [CI], -22.77 mm Hg to -2.85 mm Hg; P=.01) and diastolic blood pressure (DBP) (weighted mean difference, -5.56; 95% CI, -8.15 mm Hg to -2.97 mm Hg; P<.0001). This pooled analysis shows that for patients with resistant hypertension, RD is more effective in reducing SBP and DBP than PHAR. RD may be more effective in special subgroups of patients, which needs to be identified in future investigations.

[Study on relationship between Trp64Arg polymorphism of ß3-adrenergic receptor gene and obesity and blood lipids].

OBJECTIVE: To investigate the relationship between the Trp64Arg polymorphism of ß3-adrenergic receptor (ADRB3) gene and obesity and the levels of blood lipids in the Northern Han Chinese population. METHODS: A total of 1 602 subjects in northern Han Chinese were recruited in this study, including 995 males and 607 females. Genotyping was performed using the TaqMan assay to identify the Trp64Arg polymorphisms of the ADRB3. The relationship between the polymorphism and obesity and blood lipids was analyzed. RESULTS: The genotype distribution for Trp64Arg polymorphism was in conformity with the Hardy-Weinberg equilibrium (HWE) in the recruited population (χ² = 0.043, P = 0.087). The frequency of Arg64 allele was 15.82%. In the overall analysis, no significant association was showed between the Trp64Arg polymorphism and the Body Mass Index (BMI) or the levels of blood lipids. Subgroup analysis was performed by hypertension. In the hypertensive subgroup, the results showed significant association between the polymorphism and the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and the ratio of TC and high-density lipoprotein cholesterol (TC/HDL-C) (TC: (5.27 ± 1.04) mmol/L vs (5.10 ± 1.02) mmol/L, t = 2.334, P = 0.02; LDL-C: (3.42 ± 0.88) mmol/L vs (3.27 ± 0.87) mmol/L, t = 2.067, P = 0.039; TC/HDL: 4.81 ± 1.31 vs 4.57 ± 1.25, t = 2.563, P = 0.011). Stepwise multiple regression analysis showed that there were significant associations between the Trp64Arg polymorphism and the levels of blood lipids. The polymorphism might affect 3.2% variances of the level of TC (P = 0.030, R² = 0.032), 2.5% variances of the level of LDL-C (P = 0.030, R² = 0.025), 3.4% variances of the TC/HDL-C ratio (P = 0.001, R² = 0.034), respectively. In the normatensive subgroup, there was no significant association between the polymorphism and the levels of lipids. No significant association was observed between the polymorphism and BMI either in the hypertension group or in the normotension group. CONCLUSIONS: The Trp64Arg polymorphism in ADRB3 gene may be associated with the levels of blood lipids of the Chinese Han patients with essential hypertension. The hypertensive patients with the Trp64Trp genotype may be liable to dyslipidemia.

Association between the APOB XbaI and EcoRI polymorphisms and lipids in Chinese: a meta-analysis.

BACKGROUND: No previous meta-analysis was to report the association between the apolipoprotein B (APOB) XbaI and EcoRI polymorphisms and serum lipids in Chinese. We performed the study to investigate their potentially association. METHODS AND RESULTS: Studies in English and Chinese were found via a systematic search of Pubmed, Embase, CNKI and Wanfang databases. The dominant genetic model and random-effects model were used to pool data from individual studies. As a result, a total of 30 articles with 5611 subjects for XbaI and 2653 subjects for EcoRI were included in the current study. For the XbaI polymorphism, overall, subjects carrying X+ allele were significantly associated with higher TC,TG and LDL compared with X-X- genotype (Pvalue = 0.0006, OR (95 %) = -0.55 (-0.86,-0.23); Pvalue = 0.0004, OR (95 %) = -0.30 (-0.47,-0.14); (Pvalue = 0.05, OR (95 %) = -0.23(-0.46,-0.00), respectively). Similar results were observed in the subgroups of Han, healthy individuals (HT), coronary heart disease (CHD), cerebral infarction (CI), and cholelithiasis. For HDL, positive association between X+ allele with Lower lipid value was found in CHD and CI subgroups. For EcoRI polymorphism, overall, the E- allele carriers were found to be obviously linked with elevated LDL and lower HDL compared with E + E+ genotype (Pvalue = 0.02,OR (95 %) = -0.27 (-0.49,-0.05); Pvalue = 0.01, OR (95 %) = 0.17 (0.03, 0.30), respectively). TC was significantly high in subjects carrying E- allele in the subgroup of hyperlipidemia. No evidence of publication bias was observed. CONCLUSIONS: The two genetic variants of APOB may be associated with serum lipids in Chinese.

G-protein beta 3 subunit polymorphisms and essential hypertension: a case-control association study in northern Han Chinese.

OBJECTIVE: To explore the association between the three polymorphisms [ C825T, C1429T and G(-350)A] of the gene encoding the G protein beta 3 subunit (GNB3) and hypertension by performing a case-control study in the northern Han Chinese population. METHODS: We recruited 731 hypertensive patients and 673 control subjects (the calculated power value was > 0.8). Genotyping was performed to identify C825T, C1429T and G(-350)A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models (additive, dominant and recessive models). RESULTS: The genotype distribution and allele frequencies of C825T, C1429T and G(-350)A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C1429T and G(-350)A polymorphisms and the risk of essential hypertension in any genetic model. Linkage disequilibrium was only detected between C825T and C1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. CONCLUSIONS: Our study suggested that the GNB3 gene polymorphisms [C825T, C1429T and G(-350)A] were not significantly associated with essential hypertension in northern Han Chinese population.