血管紧张素原基因突变与原发性高血压病关系的研究进展

本文在介绍了血管紧张素原基因已知的几种突变与原发性高血压的关系的基础上,对受试者的年龄、性别、高血压病家族史和其它相关基因对研究结果的影响进行了综述,同时也讨论了该基因突变引发高血压的原因。最后就该基因突变与其它相关疾病的关系作了简要介绍。     

肾素- 血管紧张素- 醛固酮系统与原发性高血压病的关系

目的:探讨血浆肾素-血管紧张素系统与原发性高血压病的关系。方法:采用病例-对照研究设计,入选125例原发性高血压病患者与60例血压正常健康体检者为对照组。采用放射免疫方法测定立位、卧位血浆肾素活性(PRA),醛固酮(ALD)浓度及血管紧张素Ⅱ(AngⅡ)浓度。结果:原发性高血压患者,立位、卧位血浆PRA均低于正常对照组(P<0.05),而ALD浓度及AngⅡ浓度均高于正常对照组(P<0.05)。根据高血压病1级、2级、3级分组,立位、卧位血浆PRA均依次降低(P<0.05);而ALD浓度及AngⅡ浓度依次升高(P<0.05)。结论:肾素-血管紧张素-醛固酮系统与原发性高血压病的发病关系密切,血浆PRA水平、AngⅡ及ALD浓度有望成为原发性高血压病分级的有效指标;降低原发性高血压患者AngⅡ及ALD量是治疗高血压病的关键,血浆AngII、ALD也有望成为评价原发性高血压病疗效的指标。     

老年高血压病患者的高胰岛素血症与血脂及血管紧张素的关系

目的探讨老年高血压病的高胰岛素血症（ＨＩＳ）与血脂及血管紧张素（Ａｎｇ）的关系。方法比较４８例老年高血压病患者和５４例老年非高血压病患者空腹血糖、胰岛素、总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、高密度脂蛋白（ＨＤＬ）、ＡｎｇＩ、Ⅱ水平。结果老年高血压病组空腹胰岛素显著高于非高血压病组（Ｐ＜０．０１）;高血压病组ＴＧ、ＡｎｇⅡ显著增高（Ｐ＜０．０５）;高血压病组血糖、ＴＣ、ＨＤＬ、ＡｎｇⅠ与非高血压病组无明显差异（Ｐ＞０．０５）。结论老年高血压病患者存在ＨＩＳ,且脂质代谢异常,伴有ＡｎｇⅡ升高。     

血管紧张素受体的研究进展

血管紧张素Ⅱ受体（ＡＴＲ）是机体肾素－血管紧张素系统（ＲＡＳ）的重要组成分之一,介导血管紧张素Ⅱ的生理学效应,参与血管舒缩,水盐代谢和醛固酮分泌以及血管平滑肌增生和功能调节等,是ＲＡＳ系统作用于效应器的关键步骤,本文对ＡＴＲ分型,生物学效应,基因表达调控及信号转导途径进行综述。     

多个顺式作用元件调节血管紧张素原基因表达

血管紧张素原是最强的血管活性物质——血管紧张素Ⅱ的唯一前体,在不同的生理和病理条件下,其水平各异．为了研究血管紧张素原基因表达的调控,将人血管紧张素原基因５′端侧翼序列１．２ｋｂ同氯霉素乙酰转移酶（ＣＡＴ）基因编码序列连接,构成表达载体,并且在此基础上构建５′端系列缺失的突变表达载体,用这些表达载体转染ＨｅｐＧ２和ＣＯＳ－７,确定了正负调控元件;同时应用ＤＮＡ－蛋白质凝胶泳动检测技术,发现核蛋白质与该顺式元件的结合,从而证明多个顺式作用元件调节血管紧张素原基因的表达．     

血管紧张素转换酶2-血管紧张素1-7-Mas轴对血管作用的研究进展

血管紧张素转换酶2（ACE2）和Mas受体的发现使人们对肾素-血管紧张素（RAS）有了更全面的认识。ACE2可水解血管紧张素Ⅰ和血管紧张素Ⅱ直接或间接生成血管紧张素1-7（Ang 1-7）,并与高血压的形成密切相关。Ang 1-7主要通过Mas受体引起血管舒张、抑制细胞增殖。ACE2-Ang1-7-Mas轴的发现为RAS的研究、高血压等心血管疾病的防治和新药开发提供了新的思路和方向。     

血管紧张素转化酶抑制肽的研究进展

血管紧张素转化酶 (angiotensin I convertingenzyme ,ACE)在血压调节方面起着重要的作用 ,当其受到抑制时血压就会降低。许多合成的ACE抑制剂被广泛地应用于临床 ,但会造成多种副作用。近年来 ,对天然ACE抑制肽的研究表明 ,一些来源于蛋白酶解产生的活性肽可以对ACE起到有效的抑制作用。综述了血管紧张素转化酶的抑制肽的降压原理 ,种类和来源以及结构特点等的研究进展 ,并对其应用前景进行了展望。     

血管紧张素II2型受体基因缺失不影响肾素—血管紧张素系统

基于目前对血管紧张素Ⅱ２型受体（ＡＴ２）功能的认识,认为血管紧张素Ⅱ１型受体（ＡＴ１）和ＡＴ２受体有相互拮抗作用。依据上述论点,本研究利用ＡＴ２受体基因敲出小鼠,观察了ＡＴ２受体缺失后是否造成肾素－血管紧张素系统其它成分代偿性紊乱。结果发现,ＡＴ２受体基因缺失小鼠血浆和肾组织中血管紧张素Ⅱ的浓度以及肾组织中肾素、ＡＴ１Ａ受体的基因表达均未发生明显改变,表明ＡＴ２受体缺失未对肾素－血管紧张素系统产生     

抗血管紧张素原多克隆抗血清的制备及鉴定

为深入研究血管紧张素原（angiotensinogen,AGT)的表达和组织分布特征,我们以原核表达的AGT蛋白C末端片段为免疫原免疫家兔,制备了针对AGT的多克隆抗血清,并对其进行了ELISA、Western印迹分析及免疫组化鉴定。结果发现,经多次免疫后获得的多克隆抗血清不仅效价高（1：25600）,而且能特异性地针对组织内源性及原核表达的AGT蛋白,同时在人和大鼠组织AGT之间会发生交叉反应。以此抗血清进行免疫组化染色,观察到人胰腺的胰岛细胞及杆内胆管上皮细胞胞浆均有AGT蛋白表达。以上结果提示,利用大鼠杆菌融合表达的AGT蛋白可有效刺激家兔产生AGT抗体。本工作为进一步研究AGT乃至局部RAS的生理、病理意义提供了重要的实验工具。     

Association between prostaglandin E2 receptor gene and essential hypertension

BACKGROUND: Essential hypertension (EH) is a complex multifactorial polygenic disorder that is thought to result from an interaction between an individual's genetic makeup and various environmental factors. In the kidney, prostaglandins (PGs) are important mediators of vascular tone and salt and water homeostasis, and are involved in the mediation and/or modulation of hormonal action. In previous studies, mice deficient in the prostaglandin E2 (PGE(2)) EP2 receptor had resting systolic blood pressure (BP) that was significantly lower than that of wild-type controls. The BP of those mice increased when they were put on a high-salt diet, suggesting that the EP2 receptor is involved in sodium handling by the kidney. In the present study, we investigated the association between EH and nucleotide polymorphisms in the gene encoding the prostaglandin E2 receptor subtype EP2 (PTGER2). METHODS: We selected three single-nucleotide polymorphisms (SNP) in the human PTGER2 gene (rs1254601, rs2075797, and rs17197), and we performed a genetic association study of 266 EH patients and 253 age-matched normotensive (NT) controls. RESULTS: There was no significant difference in overall distribution of genotypes or alleles of any of the SNP between the EH and NT groups. However, among men, the A/A type of the SNP rs17197 (rs17197, A/G in 3'UTR) was significantly more frequent in EH subjects than in NT subjects (P=0.041). CONCLUSION: The present findings suggest that rs17197 is useful as a genetic marker of EH in men.     

The ScaI gene polymorphism of the atrial natriuretic factor and essential arterial hypertension in childhood

In order to investigate the contribution of the atrial natriuretic factor (ANF) gene in pathogenesis of essential arterial hypertension (EAH), we analyzed the ScaI gene polymorphism of the ANF gene in a group of children with EAH. Fifty-eight children, aged 8-19 years, with the diagnosis of EAH were included in the association study and were compared to 57 subjects with normal blood pressure (the control group). Arterial hypertension was defined as systolic/diastolic blood pressure higher than the 95th age-gender-height percentile of the adopted reference values. We failed to demonstrate an association between the ScaI ANF gene polymorphism and EAH in childhood (OR = 2; 95% CI 0.9-4.2; p = 0.07), however, we provided evidence of an interaction between the ScaI ANF gene polymorphism and obesity defined as BMI over the 85th percentile (OR = 13.1; 95% CI 1.6-106; p < 0.001).     

Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients

Several studies have demonstrated the importance of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms in the pathogenesis of hypertension. This study sought to determine the association between the ACE I/D polymorphism and essential hypertension in young Pakistanis. The frequency of the ACE I/D polymorphism was established by a comparative cross-sectional survey of Pakistani patients suffering from essential hypertension and ethnically matched normotensive controls. Samples were collected from tertiary care hospitals in northern Pakistan. Hypertensive individuals were defined as those with a systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg on three separate occasions, or those currently receiving one, or more, anti-hypertensive agents. DNA samples obtained from hypertensive (n = 211) and normotensive (n = 108) individuals were typed by PCR. The frequency of the ACE I/I genotype was significantly higher in hypertensive patients, aged 20-40 years, than in normotensive controls of the same age group (chi(2) = 4.0, P = 0.041). Whereas no overall significant differences were observed between the I/I, I/D and D/D ACE genotypes (One way ANOVA, F = 0.672; P = 0.413). The association between the ACE I/I genotype and essential hypertension in individuals aged 相似文献   

脲原体拓扑异构酶基因突变与喹诺酮类耐药的相关性研究

脲原体对喹诺酮类抗生素的耐药性与拓扑异构酶的基因突变有关。本研究在前期提出的棋盘稀释法脲原体药敏试验的基础上,对拓扑异构酶基因进行序列分析。结合既往的文献资料,确认了ParCS83L是脲原体喹诺酮类耐药性相关突变;而GyrAE112D和ParCT125A属于菌株的多态性表现。同时,本研究还发现了一些新的可能和喹诺酮类耐药相关的基因突变,这些突变以及多个基因突变是否存在叠加效应尚需进一步研究。     

Association study of common variations of FBN1 gene and essential hypertension in Han Chinese population

Fibrillin-1 (FBN1) was reported to have impact on the physiological arterial stiffness and vascular remodeling with hypertension of recent years. In the previous study we reported the association of four functional single nucleotide polymorphisms (SNPs) of FBN1 gene and hypertension. Here, we further investigate the association of four tagging SNPs (tagSNPs) which covered remain genetic variation blocks of FBN1 gene with hypertension, blood pressure and efficacy of antihypertensive in a South Han Chinese population. A case–control study including 2,012 hypertension cases and 2,116 controls age- and sex-matched controls was conducted from a community-based population and four candidate tagSNPs of the FBN1 gene were genotyped. Association analysis by multiple logistic regression was conducted for allele, genotype and haplotype and hypertension, blood pressure trait and control status with antihypertensive. General linear model was applied to compare blood pressure levels between genotypes. The association of rs17361868 and hypertension was statistically significant and that was further observed in female, ≥55 years, non-smoking and non-drinking populations (P < 0.05). Significant association of rs668842, rs11635140 and hypertension were observed in <55 years population as well as the later in female and non-smoking populations respectively. Haplotype G-T constructed of rs668842 and rs11635140 was significantly associated with hypertension comparing to reference haplotype A-C (P = 0.022). Normally distributed square root of TGF-β1 (pg/ml) of hypertension cases (148.56 ± 66.46) was significantly higher than that of control (128.52 ± 65.11), P = 0.008. Furthermore, TGF-β1 was significantly correlated with SBP (r = 0.135, P = 0.018) and DBP (r = 0.154, P = 0.007) respectively whereas no statistical difference of blood pressure or TGF-β1 was observed between genotypes. Remarkably, rs17361868 were significantly associated with the status of blood pressure in the patients taking three of the antihypertensive drugs, Zhen Ju Jiang Ya tablets, Jiang Ya tablet and compound reserpine (P < 0.05). The present study provides further association evidence of FBN1 gene polymorphisms and hypertension, antihypertensive efficacy. Further replication of these results via association or prospective studies conducted in other populations is warranted.     

The pathophysiology of hyperuricemia in essential hypertension: a pilot study

We have examined whether hyperuricemia in essential hypertension may be related to an increased insulin secretion thereby enhancing the tubular reabsorption of sodium and thus uric acid. Insulin hypersecretion, as elicited by the oral glucose tolerance test (OGTT), increased a mean of 5-fold in 12 essential hypertensive patients. Urinary uric acid to creatinine ratio significantly diminished by a mean of 62% after the OGTT. Simultaneously, urinary sodium to creatinine ratio decreased by a mean of 54%. These results suggest that insulin may mediate uric acid underexcretion due to its tubular sodium retaining effect in essential hypertensive patients.     

Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension

Even if the importance of angiotensinogen (AGT) gene has been known in gene targeting animals and humans genetic studies, its precise mechanism and the interaction among AGT gene variants, plasma AGT concentration and risk for hypertension remain uncertain. We examined whether AGT gene variants predispose to hypertension via an increase of plasma AGT concentration. Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA. Using 9 AGT gene variants which included new polymorphisms (G-152A and T+31C), we examined the association with hypertension and with plasma concentration by a case-control study. Haplotype analysis revealed that G-6A, T+31C and M235T polymorphisms were in absolute linkage disequilibrium and were associated with hypertension but not with plasma AGT level. On the other hand, -1074t;T235 haplotype was associated with an increase of AGT level but not with hypertension. In the haplotype analysis, only H3 haplotype frequency, which contained G-6, T+31 and M235 alleles, was significantly increased in normotensive subjects, suggesting that this haplotype is associated with a hypotensive effect. According to combined haplotype analysis of diallele and microsatellite markers, it remains a possibility that M235T, T+31C, G-6A, A-20C and G-1074T polymorphisms may play an important role in increased risk for essential hypertension. Our results suggest that the positive association between AGT polymorphism and hypertension is not simply explained by an increase of plasma AGT concentration.