Association of angiotensinogen gene M235T polymorphism with the risk of IgA nephropathy: a meta-analysis

The association between angiotensinogen (AGT) M235T gene polymorphism and IgA nephropathy (IgAN) risk remains elusive. Our aim was to evaluate the association between AGT M235T gene polymorphism and IgAN susceptibility by performing a meta-analysis. Eligible studies were searched according to predefined criteria using electronic databases. Eight studies were identified for the analysis of the association between AGT M235T gene polymorphism and IgAN risk. M allele/MM genotype were not associated with IgAN risk in overall populations, Caucasians and Asians (overall populations: p?=?0.448 and 0.861, Caucasians: p?=?0.618 and 0.886, Asians: p?=?0.566 and 0.652). TT/MT genotype were not associated with IgAN risk in overall populations, Caucasians and Asians (overall populations: p?=?0.703 and 0.454, Caucasians: p?=?0.975 and 0.946, Asians: p?=?0.697 and 0.353). No evidence of publication bias was observed. In conclusion, AGT M235T gene polymorphism may not be correlated with IgAN susceptibility in overall populations, Caucasians and Asians. However, more studies should be performed in the future.     

AGT基因型对贝那普利降压疗效的影响

目的研究原发性高血压(EH)患者的血管紧张素原(AGT)基因M235T多态性与贝那普利降压疗效的相关性。方法251例EH患者口服贝那普利10～20mg/d,进行为期6周的降压治疗。用聚合酶链反应(PCR)和限制性酶切方法检测所有患者的AGT基因M235T多态性,按MM、MT和TT三种基因型分组。治疗前后及治疗过程中对患者的收缩压(SBP)和舒张压(DBP)等进行监测,以比较不同基因型患者之间的降压疗效。结果基因型为MM、MT及TT者分别为23例(9.2%)、104例(41.4%)和124例(49.4%);在251例患者中,MM、MT及TT三组患者间治疗后SBP和DBP的降幅差异无统计学意义(P>0.05);按年龄分层进行的亚组分析显示:在≥60岁的老年亚组中,治疗后MM、MT及TT三组患者DBP的降幅分别为(14.8±4.8)mmHg,(7.9±7.7)mmHg和(9.8±6.4)mmHg(P=0.034),MM较MT和TT组的DBP降幅大。结论本研究显示,老年(≥60岁)EH患者的AGTM235T多态性与贝那普利降压疗效相关,提示特定的基因多态性可能会影响某些降压药物的疗效。     

Role of microRNA-29a in the development of diabetic retinopathy by targeting AGT gene in a rat model

Objectives

This study intends to explore the role of microRNA-29a (miRNA-29a) in the development of diabetic retinopathy by targeting AGT gene in a rat model.

血管紧张素原T704Crs699位点多态性与小动脉粥样硬化性脑梗死发病机制的关系研究

目的 探讨血管紧张素原（AGT）T704Crs699位点多态性与小动脉粥样硬化性脑梗死（SA）发病机制的关系。方法 以SA组186例和对照组94例为研究对象,采用SNaPshot技术及GeneMapper4.0软件分析AGTT704Crs699位点的基因分型情况,比较C（T）基因特征及等位基因频率,并进一步采用多元logistic回归,分析脑血管病常见危险因素与所携带基因分型在SA发病中的交互作用。结果AGTT704Crs699位点在SA组中以携带TT和TC基因型多见（30.1%、41.9%）,但患病率以CC基因型为高（80.0%）,与TT和TC基因型（65.1%、60.4%）比较,差异均有统计学意义（字2=5.24、6.78,均P＜0.05）;SA组T等位基因频率高于C等位基因频率,但差异无统计学意义（字2=1.23,P＞0.05）。携带AGTCC基因型（OR=3.34,95%CI1.54～8.43）、高血压病史（OR=5.59,95%CI2.35～22.61）、老龄（≥70岁）（OR=2.82,95%CI1.13～10.63）是SA发病的独立危险因素。结论AGTT704C基因多态性可能是SA发病机制的遗传因素,且携带AGTCC基因型,高血压病史和老年患者具有协同致病效应。     

肾素和血管紧张素原基因多态性与脑梗死的关系

目的研究肾素（REN）基因G10631A、血管紧张素原（AGT）基因T704C、C521T单核苷酸多态性与脑梗死的关系。方法选择180例脑梗死患者和130例健康对照者,采用聚合酶链式反应-限制性片段长度多态性（PCR—RFLP）技术,检测REN基因G10631位点、AGT基因T704、C521位点基因型和等位基因,比较两组基因型及等位基因频率的差异。并运用Logistic回归分析脑梗死的危险因素。分析该人群单倍型结构,以期在本组人群中发现脑梗死相关的多态组合。结果①脑梗死组REN 10631 AA基因型频率（31．7％）及A等位基因频率（49．4％）高于对照组（10．0％和30．3％）,差异有统计学意义,P〈0．05。②脑梗死组AGT704CC基因型频率（63．3％）及C等位基因频率（79．7％）高于对照组（34．6％和61．2％）,差异有统计学意义,P〈0．05。③脑梗死组AGT521TF基因型频率（21．7％）及T等位基因频率（27．8％）高于对照组（6．9％和11．9％）,差异有统计学意义,P〈0．05。④经多因素Logistic回归分析,REN 10631AA基因型、AGT704CC基因型、AGT521IT基因型可以增加脑梗死的发生概率,发病的相对危险度（OR）分别为2．617（95％CI：1．033～6．628）、2．699（95％CI：1．274—5．716）、3．362（95％CI：1．266～8．934）,差异有统计学意义,P〈0．05。⑤单倍型521T-10631A-704C在脑梗死组的分布频率高于健康对照组（P=0．000）。结论REN 10631AA基因型和A等位基因、AGT704CC基因型和c等位基因、AGT 521TF基因型和T等位基因可能为脑梗死的易患因素。单倍型521T-10631A-704C可能是脑梗死发病的遗传危险因素。     

Further Studies on the Noradrenergic and the Renin Angiotensin Systems in the Brain of the Rat

Previous investigations have shown that depletion of brain norepinephrine (NE) induced by chemical sympa thectomy resulted in significant changes in the central renin-angiotensin system. The purpose of the present work was to increase the NE concentration in the central nervous system (CNS) in order to analyze its effect on the peptidergic complex and on the blood pressure (BP) levels. Treated rats were given the following drugs in the drinking water: 1-dopa (12 mg/rat/day), carbidopa (6 mg/rat/day) and pargyline (10 mg/rat/day) during 25 days. BP was determined, blood and cerebrospinal fluid (CSF) samples were obtained. The CNS was dissected into several areas. NE, angiotensinogen (AoC) and renin concentration (RC) were determined in the brain parenchyma; AoC was evaluated in CSF and plasma samples. Pharmaco-logical treatment resulted in an hypotensive effect and, at the same time, an increase of NE in the CNS (about 100 %; pCO .0005). These changes were accompanied by a significant decrease in the peripheral and central AoC. These results add new evidence to the postulated relationship between these two important regulatory systems involved in cardiovascular control.     

Renin-angiotensin-system gene polymorphisms and depression

Given the abundance of the renin-angiotensin system (RAS) components in the brain, their importance in behavior and cognition, and the data that implicates them in the etiology and treatment of depression, it is possible that those RAS gene polymorphisms associated with increased RAS activity may also be associated with depression. The frequencies of common polymorphisms of genes encoding for components of the RAS, namely angiotensinogen (M235T), angiotensin converting enzyme (ACE) (insertion, I; deletion, D), angiotensin receptor type I (A1166C), and angiotensin receptor type II (C3123A) were determined in DNA extracted from buccal cells from a Lebanese population of 132 depressed patients and their first-degree relative case-controls. The angiotensin receptor type 1 (A1166C) CC genotype was significantly associated with depression (p=0.036). None of the other common RAS-associated polymorphisms were significantly associated. The results support the hypothesis that increased RAS activity may increase relative risk of depression in that the angiotensin receptor type 1 (A1166C) CC genotype is associated with increased responsiveness to angiotensin II.     

血管紧张素原基因核心启动子多态性与原发性高血压相关性的研究进展

原发性高血压是由环境因素、生活方式和遗传因素共同作用引起的一种多基因遗传病,其发病机制比较复杂。目前关于AGT基因核心启动子多态性与原发性高血压的关系,国内外的研究报道尚有争议,但大部分研究结果支持二者有相关性。本文就AGT基因核心启动子多态性与原发性高血压相关性的研究进展予以综述,以期为原发性高血压的发病机制和防治提供科学依据。     

Modulation of Tissue Angiotensinogen Gene Expression by Glucocorticoids,Estrogens, and Androgens in Shr and Wky Rats

Local or tissue renin angiotensin systems are thought to participate in cardiovascular regulation. However, little information is available on the mechanisms by which renin and angiotensinogen synthesis and secretion are regulated in these tissues. In view of the importance of steroid hormones in the regulation of hepatic angiotensinogen, we have examined the effects of dexamethasone, ethinyl estradiol, or dihydrotestosterone on angiotensinogen gene expression in peripheral or cerebral tissues of Wistar Kyoto (WKY) or spontaneously hypertensive rats (SHR). Following a single injection of dexamethasone (7 mg/kg) the concentrations of angiotensinogen mRNA increased in nearly all organs examined. The differences to controls were higher in SHR than in WKY. Dexamethasone in low doses (10 μg/kg/day) given for 10 days did not alter angiotensinogen mRNA or blood pressure in control animals, but increased both parameters in the hypertensive strain. The reponse to a single dose of ethinyl estradiol (3 mg/kg) was not as uniform as that to dexamethasone, and a tendency for a higher sensitivity was found in SHR. High stimulation rates were found in liver and kidneys of both strains. A single dose of dihydrotestosterone (10 mg/kg) did not significantly affect angiotensinogen mRNA in any organ. Only when a high dose of 50 mg/kg was given daily for 20 days, was angiotensinogen mRNA increased in some tissues. These data indicate that glucocorti-coids and estrogens participate in the regulation of angiotensinogen gene expression in several extrahepatic tissues. The higher sensitivity to glucocorticoids in SHR may be relevant for the developement of hypertension in this strain.