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.

[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 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.

[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.

[Pericardial endothelin secretion in patients underwent open heart surgery.].

OBJECTIVE: To evaluate pericardial endothelin (ET) secretion by the human pericardial mesothelial cells. METHODS: Plasma, pericardial fluid and pericardial tissue were obtained in 51 patients receiving open heart surgery (coronary artery bypass grafting, elective heart valvuloplasty or valve replacement). ET concentrations in the plasma, pericardial fluid and pericardial tissues were measured by radioimmunoassay (RIA). ET mRNA expression in the human pericardium was detected by in situ hybridization. RESULTS: (1) The levels of ET in human pericardial fluid was significantly higher than that in the plasma [(128.8 +/- 44.0) ng/L vs. (93.7 +/- 28.6) ng/L, P < 0.001]; (2) ET concentration in the pericardial tissue was (510.3 +/- 156.7) ng/kg; (3) In situ hybridization technique evidenced the abundant ET mRNA expression in human pericardial mesothelial cells. CONCLUSION: The study indicated that pericardium secreted ET into the pericardial space.

[Increased plasma vasoactive substances and antioxidant enzymes levels in prehypertensive patients].

OBJECTIVE: This study investigates the plasma vasoactive substances and antioxidant enzymes levels in prehypertensive patients. METHODS: Patients were scruited according to JNC-7 and divided into three groups: 74 normotensive subjects (NT group, 38 males, mean age 47.15 +/- 7.77 years old); 51 prehypertensive patients (PH group, 29 males, mean age 47.82 +/- 5.16 years old) and 71 essential hypertensive patients (EH group, 37 males, mean age 48.25 +/- 7.97 years old). Serum lipids and plasma angiotensin II (Ang II), endothelin (ET), vasopressin (AVP), calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GPX) by radioimmunoassay and enzyme linked immunosorbent assay. RESULTS: Serum Lipids (TG, CHO and LDL) were significantly higher in the PH and EH groups compared to NT group (all P < 0.05). Ang II, AVP and ET were significantly increased while CGRP decreased in the EH group than that in NT group (all P < 0.05). SOD was significantly lower while GPX significantly higher. Further more, in the PH and EH groups than those in the NT group (all P < 0.05). CONCLUSION: SOD was reduced and GPX increased in prehypertensive patients.

[Hyperplasia suppressor gene expression in vascular smooth muscle cells derived from normotensive and hypertensive patients underwent bypass surgery].

OBJECTIVE: To investigate the novel hyperplasia suppressor gene (HSG) expression in vascular smooth muscle cells derived from normotensive and hypertensive patients underwent bypass surgery. METHODS: Coronary heart disease patients underwent coronary artery bypass graft (CABG) operation in BEIJING ANZHEN hospital from 4 - 9, 2006 were enrolled in this study and divided into hypertensive group (n = 28) and normotensive group (n = 26). The preoperative venous blood samples were taken for serum biochemical and vasoactive peptides measurements. Total RNA was extracted from WBC, explanted-vessels and cultured VSMCs using TRIZOL and HSG expression was determined by Semi-Quantitative RT-PCR. RESULTS: Body mass index (BMI) was significantly higher in hypertensive group compared to normotensive group (P < 0.01) while other biochemic parameters and vasoactive peptides were similar between the groups. BMI and GLU, BMI and SBP, BMI and DBP, GLU and TG, SBP and DBP were positively correlated (all P < 0.05). HSG expression in WBC, VSMCs and vessel tissue were significantly lower in hypertensive group than those in normotensive group (all P < 0.05). HSG expression in tissue was negatively correlated to BMI, SBP and DBP (all P < 0.05). CONCLUSIONS: Reduced HSG expression and the negative correlation on vascular tissue HSG expression to BMI, SBP and DBP suggested a possible inhibitory role of HSG on VSMC proliferation and blood pressure.

[Relationship of the HSG gene single nucleotide polymorphism and hypertension].

OBJECTIVE: To investigate the single nucleotide polymorphism (SNP) of the novel hyperplasia suppressor gene (HSG) to uncover the relationship between HSG SNP and hypertension. METHODS: Totally, 74 normotensive people (38 men and 36 women), 51 patients with essential hypertension (27 men and 24 women) and 20 hypertensive patients with family history of essential hypertension (9 men and 11 women) were chosen, with mean ages of (54 +/- 8) years, (57 +/- 8) years and (38 +/- 22) years, respectively. Peripheral venous blood specimen was collected from each of them and then DNA was extracted. The right primers were designed for DNA amplification with PCR. Each of the PCR-products from different groups was sequenced by ABI PRISM 377-DNA sequencer and their base components and characteristics of the same fragment were compared each other. RESULTS: Blood levels of creatinine (CRE) and urea nitrogen (BUN) were significantly higher in the hypertensives than in the normotensives (P < 0.01). Systolic and diastolic blood pressures were significantly higher in the hypertensives and the hypertensives with family history of essential hypertension than in the normotensives (P < 0.01 and P < 0.05). There existed three kinds of SNP in the HSG 12th intron (1q82139 G/A, 82153C/G and 82273G/-), and there was significant difference in 1q82153C/G and 82273G/- SNP between the hypertensives and normotensives (P < 0.05 and P < 0.01) and between the hypertensives with family history and the normotensives (P < 0.01 and P < 0.01). And, the similar difference in C/G allele and G deletion could be found in different populations. Moreover, the CC genetype of 1q82153 was common in the population (P < 0.01) and G deletion was more common in Chinese Han people with family history of essential hypertension. There was no significant difference existed in 1q82139 G/A mutation among the three groups. CONCLUSIONS: Measurements of renal function indicators (CRE and BUN) could probably reflect earlier advance of hypertension and damage to target organs. There existed three kinds of mutation in the 12th intron of the HSG 1q82139 G/A, 82153 C/G and 82273 G/-. The 1q82139 G/A could be a nonsense mutation and there was significant difference in the 1q82153 C/G and 1q82273 G/- SNP and gene frequencies between different Chinese Han populations, which could be independent risk factors for essential hypertension.