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.

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.

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.

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.

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.

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.

The association between the polymorphisms in a sodium channel gene SCN7A and essential hypertension: a case-control study in the Northern Han Chinese.

Nax , an α-subunit of the sodium channel encoded by the SCN7A gene, has been deemed to be a sensor of the concentration of sodium in the brain and may be involved in salt intake behavior. We inferred that Nax /SCN7A may participate in the regulation of blood pressure and the pathogenesis of essential hypertension (EH). The present case-control study involving 615 hypertensives and 617 normotensives was performed to investigate the association between SCN7A polymorphisms and EH in the Northern Han Chinese population. The three common single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the exons of SCN7A were genotyped with the TaqMan assay. Significant association between SNP rs7565062 and EH was found under the addictive and dominant genetic models (P = 0.024, OR = 1.283, 95%CI [1.033-1.592]; P = 0.013, OR = 1.203, 95%CI [1.040-1.392]; respectively). The three SNPs were in close pair-wise linkage disequilibrium with each other and the haplotype analyses indicated that haplotype G-A-T was significantly associated with increased risk of EH (P = 0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A was significantly associated with EH and the allele T of rs7565062 or the related haplotype G-A-T will be a genetic risk factor for EH in the Northern Han Chinese population.

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.

The association between endothelial nitric oxide synthase gene G894T polymorphism and hypertension in Han Chinese: a case-control study and an updated meta-analysis.

UNLABELLED: Abstract Background: The G894T (rs1799983) polymorphism in endothelial nitric oxide synthase (eNOS/NOS3) gene has been implicated in susceptibility to essential hypertension (EH) in some studies, but no clear consensus has been reached in the Chinese population. AIMS: This study aimed to investigate the association of the G894T polymorphism and EH in Han Chinese. SUBJECTS AND METHODS: First, a case-control study was performed involving 1525 subjects in northern Han Chinese to study the association between G894T variants and EH and then a meta-analysis was conducted of all available studies in Han Chinese. A total of 25 studies comprising 13,443 subjects were finally included in this meta-analysis. RESULTS: The present case-control study failed to show significant association of G894T variant with EH in northern Han Chinese. The subsequent meta-analysis showed that this polymorphism might be associated with EH in Han Chinese (p < 0.001, OR = 1.32), especially in southern Han Chinese (p < 0.001, OR = 1.59), but not in northern Han Chinese (p = 0.12, OR = 1.16). The meta-regression analysis suggested that the geographic difference of subjects was related to heterogeneity (p = 0.029). CONCLUSIONS: The relationship between the G894T polymorphism and hypertension in Han Chinese may be attributed to the difference in geographic background of subjects. It is necessary to carry out further research with a large sample size and focusing on gene-environment interactions.

[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.

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and lung cancer risk: a meta-analysis.

No clear consensus has been reached on the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung cancer risk. We performed a meta-analysis to summarize the possible association. We conducted a computer retrieval of PubMed and Embase databases prior to May 2013. References of retrieved articles were also screened. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. According to the inclusion criteria, 25 articles (32 studies) were finally included. There was no statistical association between C609T polymorphism and lung cancer risk in overall, East Asians, African Americans, or Hispanics. In Caucasians, a significant association was found in allele comparison model (T vs. C) (P = 0.04, OR = 1.09, 95% CI 1.00-1.19, P(heterogeneity) = 0.24, fixed-effects model). In the subgroup of squamous cell carcinoma, a borderline significance could be found in the dominant genetic model (TT + CT vs. CC) (P = 0.05, OR = 1.20, 95% CI 1.00-1.43, P(heterogeneity) = 0.65, fixed-effects model). Significant association could also be found in allele comparison (T vs. C) (P = 0.03, OR = 1.21, 95% CI 1.01-1.44, P(heterogeneity) = 0.68, fixed-effects model). In the subgroup of small cell lung cancer risk, significant association were found in allele comparison (T vs. C) (P = 0.03, OR = 1.68, 95%CI 1.05-2.68, P(heterogeneity) = 0.10, random-effects model) and in the homozygote comparison (TT vs. CC) (P = 0.02, OR = 2.79, 95% CI 1.14-6.85, P heterogeneity = 0.72, fixed-effects model). No association was observed in adenocarcinoma subgroup. Our study suggested that NQO1 C609T polymorphism might associate with lung cancer risk in Caucasians. This polymorphism might also associate with squamous cell carcinoma and small cell lung cancer risk.

ß1-adrenoceptor gene Arg389Gly polymorphism and essential hypertension risk in general population: a meta-analysis.

The ß1-adrenoceptor (ADRB1) gene Arg389Gly polymorphism has been extensively studied as a candidate gene in essential hypertension (EH), but no consensus has been reached on the relationship between this polymorphism and EH risk. To systematically explore their possible association, a meta-analysis was conducted. All relevant case-control trials in English-language publications before 1 June 2012 were identified by searching the PubMed and Embase databases. Finally, eight articles met our inclusion criteria, including a total of 5,088 patients with EH and 6,515 controls. No evidence of publication bias was found. Fixed-effects model and random-effects model were applied for dichotomous outcomes to combine results from individual studies. Overall, the Gly allelic frequency of Arg389Gly polymorphism was significantly lower in EH subjects than that in controls (Gly versus Arg: P = 0.04, OR = 0.89, 95 % CI [0.80-1.00], P heterogeneity = 0.03, I (2) = 52 %, random-effects model; GlyGly + ArgGly versus ArgArg: P = 0.02, OR = 0.86, 95 % CI [0.76-0.97], P heterogeneity = 0.08 and I (2) = 42 %, random-effect model). Subgroup analysis by ethnicity detected this association only in East Asians. In sensitivity analysis, the study by Bengtsson K was recognized as the main cause of heterogeneity, which was the only one study with the diagnostic standard for EH as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg. We concluded that the Gly allele of ADRB1 Arg389Gly polymorphism might confer lower risk for EH, especially in East Asians.

[Associations between G1165C and A145G polymorphism of ß1-adrenoceptor and resting heart rate in the Northern Han Chinese].

OBJECTIVE: To systematically investigate the possible associations between G1165C and A145G polymorphism of ß1-adrenoceptor (ADRB1) and resting heart rate (HRrest) in Northern Han Chinese. METHODS: HRrest of 700 healthy Northern Han Chinese were measured in the sitting position.SNPs were genotyped by the TaqMan assay.Genotypes were differentiated by analyzing the fluorescence levels of PCR products using an ABI Prism 7900HT Sequence Detector. RESULTS: HRrest was significantly lower in A145G AA carriers than in AG and GG carriers (all P < 0.01) . Multiple linear regression analysis showed that age, smoking habits, systolic blood pressure, triglyceride, serum creatinine and A145G polymorphism were associated with HRrest (P < 0.01) . A145G was significantly related with HRrest independent of other possible confounding variables, and the partial regression coefficient was 2.148 (P < 0.05) . After adjusting for other confounding factors, significant association between A145G and HRrest was only found in male subjects (P < 0.05) but not in female subjects (P > 0.05) . CONCLUSION: The A145G polymorphism of ADRB1 gene is associated with HRrest in Northern male Han Chinese.

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.

Dysregulation of HSG triggers vascular proliferative disorders.

Vascular proliferative disorders, such as atherosclerosis and restenosis, are the most common causes of severe cardiovascular diseases, but a common molecular mechanism remains elusive. Here, we identify and characterize a novel hyperplasia suppressor gene, named HSG (later re-named rat mitofusin-2). HSG expression was markedly reduced in hyper-proliferative vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rat arteries, balloon-injured Wistar Kyoto rat arteries, or ApoE-knockout mouse atherosclerotic arteries. Overexpression of HSG overtly suppressed serum-evoked VSMC proliferation in culture, and blocked balloon injury induced neointimal VSMC proliferation and restenosis in rat carotid arteries. The HSG anti-proliferative effect was mediated by inhibition of ERK/MAPK signalling and subsequent cell-cycle arrest. Deletion of the p21(ras) signature motif, but not the mitochondrial targeting domain, abolished HSG-induced growth arrest, indicating that rHSG-induced anti-proliferation was independent of mitochondrial fusion. Thus, rHSG functions as a cell proliferation suppressor, whereas dysregulation of rHSG results in proliferative disorders.

[Association of C602A and T1559C polymorphisms of E-selectin gene and essential hypertension].

OBJECTIVE: To investigate the possible genetic associations between the C602A and T1559C polymorphisms of E-selectin (SELE) and essential hypertension. METHODS: Essential hypertensive patients (n = 500) and healthy normotensive subjects (n = 930) were screened for the genotypes C602A and T1559C by real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the SELE gene. RESULTS: Normotensive subjects and hypertensive patients were significantly different with respect to the genotypes CC, CA and AA, 26 (5.2%), 20 (4.0%) and 454 (90.8%) vs 14 (1.5%), 53 (5.7%) and 863 (92.8%) respectively of C602A. And the C-allele frequency was also significantly different between the NT and EH groups (C, A = 7.2%, 92.8% vs 4.4%, 95.6%). When subgrouped by gender, frequency of CC, CA, AA between normotensive and essential hypertensive males was 14 (4.7%), 11 (3.7%), 272 (91.6%) and 10 (1.7%), 34 (5.8%), 545 (92.5%), which differed significantly (P < 0.05), while in female groups, all the frequency of genotypes were significantly different (P < 0.01) except CC + CA. The additive model (TT, TC, CC) of the T1559C genotype was significantly different between essential hypertensive and normotensive groups overall, 57 (11.4%), 200 (40.0%), 43 (48.6%) and 66 (7.1%), 354 (38.1%), 510 (54.8%), respectively. The T-allele of hypertensive patients significantly differed from normotensive subjects (T, C = 31.4%, 68.6% vs 26.1%, 73.9% respectively). When subgrouped by gender, between the male NT and EH groups, the TT, TC and CC frequency of T1559C were 36 (5.9%), 117 (39.4%), 144 (48.5%) and 35 (5.9%), 230 (39.0%), 354 (55.0%), and the frequency of T vs C was 31.4% vs 68.6% and 26.1% vs 73.9%, which were significantly different (all P < 0.01). As in female NT and EH groups, there were not significant differences existed at all. CONCLUSION: C602A and T1559C of SELE are associated with essential hypertension in the Chinese population, and T1559C is closely related with male hypertension other than in females.

[Relationship between genetic polymorphisms of ß2-adrenergic receptor gene and essential hypertension risk among the Han Chinese population: a Meta analysis].

OBJECTIVE: To evaluate the relationship between A46G and C79G polymorphisms in the ß2-adrenergic receptor (ADRB2) gene and the incidence of essential hypertension (EH) among the Han Chinese population. METHODS: We conducted a computer retrieval of PUBMED, EMBASE, CNKI, Wanfang and VIP databases prior to May 2010. Articles investigating the relationship of EH and ADRB2 gene polymorphism of Han group were found through literature search, including 15 articles on A46G and 10 articles on C79G. According to the including and excluding criteria, a Meta-analysis was conducted in EH and ADRB2 gene polymorphism of A46G and C79G. The association was examined by RevMan4.2 software through quantitative analysis. RESULTS: Eight articles on A46G polymorphism (including 1078 EH cases and 788 control subjects) and six articles on C79G polymorphism (including 1367 EH cases and 1006 control subjects) were included in the current study. Meta-analysis showed that there was a significant association between A46G polymorphism and EH: genotype GG/(AA + AG) (fixed-effected model, OR = 1.35, 95%CI = 1.04 - 1.74, P = 0.02), genotype GG/AA (fixed-effected model, OR = 1.41, 95%CI = 1.06 - 1.89, P = 0.02). No significant association was found between C79G polymorphism and EH of Han group in China: G/C allele comparison (random-effected model, OR = 0.88, 95%CI = 0.55 - 1.39, P = 0.57). CONCLUSION: Significant association was found between A46G polymorphism of ADRB2 gene and EH, whereas no association could be found between C79G polymorphism and EH among Han Chinese population.

E-selectin gene polymorphisms are associated with essential hypertension: a case-control pilot study in a Chinese population.

BACKGROUND: Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension. METHODS: Hypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study. RESULTS: Hypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C). CONCLUSION: C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.

[Plasma proteomic analysis in male normotensive, prehypertensive and hypertensive subjects].

OBJECTIVE: To compare the plasma proteome among male normotensive, prehypertensive, and hypertensive subjects. METHODS: Plasma proteome was analyzed by two-dimensional electrophoresis combined with MALDI-TOF mass spectrometry in this case-control study among well matched male normotensive, prehypertensive and hypertensive subjects (n = 26 each). RESULTS: The results showed that there were 22 differentially expressed protein spots among the protein samples derived from the 3 groups which corresponded to 18 proteins associated with inflammation and immunity, lipid metabolism, transport, coagulation and fibrinolysis, cell proliferation and apoptosis, and antioxidation. CONCLUSION: Proteins were differentially expressed in male subjects with various blood pressure levels.