Correlation between angiotensinogen gene and primary hypertension with cerebral infarction in the Li nationality of China

Objective To investigate the relationship of four single nucleotide polymorphism （SNP） haplotypes in the angiotensinogen （AGT） gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China. Methods Total 300 subjects were allocated into three different groups： Groupl, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four poly- morphisms at position - 152 （G-A）, -20 （A-C）, - 18 （C-T）, and -6 （A-G） in the promoter region of AGT. Results The frequen- cies ofCT genotype of AGT-18 and T allele in Group 1 （P = 0.003, P = 0.004） and Group 2 （P = 0.002, P = 0.002） were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group （P = 0.016）, while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 （P = 0.003） compared with the control group, while H5 haplotype frequency which included -20C and -18T was signifi- cantly increased in Group 1 （P = 0.006） versus the control. Conclusion The -20 （A-C） and - 18 （C-T） of the AGT may play an important role in pathogenesis of primary hypertension; and -20 （A-C）, -18 （C-T）, and -6 （A-G） may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Halnan, China.

Angiotensinogen Expression Is Enhanced in the Progression of Glomerular Disease

Intrarenal renin-angiotensin system (RAS) activation plays a critical role in the development and progression of renal injury. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by multiple independent mechanisms. Angiotensinogen (AGT) is the only known substrate for renin that is a rate-limiting enzyme of the RAS. Recently, enhanced intrarenal AGT levels have been shown to reflect the intrarenal RAS status in hypertension, chronic glomerular disease and diabetic nephropathy. In this review, we focus on AGT expression of the diseased glomeruli in the progression of glomerular disease. An anti-glomerular basement membrane nephritis rat model developed progressive proteinuria and glomerular crescent formation, accompanied by increased macrophage infiltration and glomerular expression of AGT and Ang II. The addition of Ang II type 1 receptor blocker to CC-chemokine recaptor 2 antagonist markedly attenuated the induction of macrophage infiltration, AGT and Ang II, and reduced glomerular crescent formation. Next, the levels of glomerular AGT expression and marker of reactive oxygen species in Zucker diabetic fatty (ZDF) obese rats were higher than those in ZDF lean rats. Hydrogen peroxide (H2O2) induced an increase in the AGT expression in primary rat mesangial cells. Furthermore, the H2O2-induced upregulation of AGT was inhibited by a mitogen-activated protein kinase kinase and a c-Jun N-terminal kinase inhibitor. These data suggest the potential contribution of enhanced AGT expression in glomeruli to the intrarenal RAS activation for the development of glomerular disease.

Angiotensinogen gene polymorphism and ischemic stroke in East Asians:A meta-analysis

OBJECTIVE： To investigate the association between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians. DATA RETRIEVAL： A computer-based online search was conducted in PubMed, Google scholar, China National Knowledge Infrastructure database between January 1990 and April 2012 for relevant studies. The key words were angiotensinogen or AGT, polymorphism or genetic and ischemic stroke or cerebral infarction. SELECTION CRITERIA： Case-controlled studies addressing the correlation between angiotensinogen gene M235T polymorphism and ischemic stroke in East Asians were included. The distribution of genotypes in the included studies was tested for Hardy-Weinberg equilibrium. Quality evaluation of the included studies was conducted by two physicians. Statistical analyses were carried out using Stata 12.0 software for meta-analysis. Heterogeneity tests, sensitivity analysis and publication bias were also conducted. MAIN OUTCOME MEASURES： The association between angiotensinogen gene M235T polymorphism and ischemic stroke risk in East Asians was assessed. RESULTS： Six relevant studies involving 891 patients with ischemic stroke and 727 controls were included in this meta-analysis. Results showed that there was a significant association between angiotensinogen gene M235T polymorphism and the risk of ischemic stroke in East Asians （T vs. M odds ratio （OR） = 1.54, 95% confidence interval （CI） = 1.10-2.16; TT vs. MM： OR = 2.24, 95%CI = 1.37-3.66; TT vs. MT： OR = 1.76, 95%CI = 1.41-2.20; MM ＋ MT vs. TT： OR = 0.57, 95%CI -= 0.46-0.70）. Sensitivity analysis confirmed that the study results were stable and reliable, with no publication bias. CONCLUSION： The angiotensinogen gene M235T polymorphism is associated with ischemic stroke in East Asians, and the TT genotype and T allele are risk factors for ischemic stroke.

Low expression of angiotensinogen and dipeptidyl peptidase 1 in saliva of patients with proliferative verrucous leukoplakia

AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.

Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma

The expression and function in growth and apoptosis of the renin-angiotensin system(RAS)was evaluated inhuman glioblastoma.Renin and angiotensinogen(AGT)mRNAs and proteins were found by in situ hybridisationand immunohistochemistry in glioblastoma cells.Angiotensinogen was present in glioblastoma cystic fluids.Thus,human glioblastoma cells produce renin and AGT and secrete AGT.Human glioblastoma and glioblastoma cellsexpressed renin,AGT,renin receptor,AT(2)and/or AT(1)mRNAs and proteins determined by RT-PCR and/

Binge ethanol intake in chronically exposed rat liver decreases LDL-receptor and increases angiotensinogen gene expression

AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human scenario. METHODS: Rats were chronically treated with ethanol in liquid diet for 4 wk followed by a single binge mode of ethanol administration (5 mg/kg body weight). Samples were processed 4 h after binge ethanol administration (chronic ethanol binge). Control rats were fed isocaloric diet. In the control for binge, ethanol was replaced by water. Expression of mRNA for angioten-sinogen, c-fos and LDL-receptor, and nuclear accumulation of phospho-extracellular regulated kinases (ERK)1/2 and ERK1/2 protein were examined. RESULTS: Binge ethanol administration in chronically treated rats caused increase in steatosis and necrosis. Chronic ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic ethanol-binge increased mRNA expression of angiotensinogen and c-fos. CONCLUSION: Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL-receptor and angiotensinogen genes, both cardiovascular risk factors.

Effects of angiotensinogen gene polymorphisms on the risk of coronary heart disease in the Chinese population： a meta-analysis

Objective Coronary heart disease （CHD） is a multifactorial disease. This meta-analysis was performed to evaluate the relationship between angiotensinogen gene polymorphisms and CHD in the Chinese population. Methods We searched literature in pubmed （1990- 2010.8） and CNKI （1990-2010.8） for all the relevant studies on 2 angiotensinogen polymorphisms （M235T and T174M） and risk of CHD. The meta-analysis software Stata 10.0 was used for ascertaining heterogeneity among individual studies and for combining all the studies. Furthermore,Egger＇s test and sensitivity analysis were performed to insure authenticity of the outcome.Results Ten associations studies on 2 angiotensinogen polymorphisms （M235T and T174M） were included in this meta-analysis. In a combined analysis, the summary per-allele odds ratio for CHD of the M235T polymorphism was 1.374 （95% confidence interval, 1.019 to 1.852） and T174M polymorphism was 4.089 （95% confidence interval, 1.697 to 9.851）. Conclusions The M235T polymorphism had weak but statistically significant association with CHD while the T174M polymorphism was more strongly associated with a CHD risk in Chinese population, but further confirmation studies are needed

Association of Polymorphisms of β_3-Adrenergic Receptor,Angiotensinogen and Angiotensin- Converting Enzyme Gene with Hypertension in type 2 DM

ObjectiveTo explore the relationship between the mutant genes of ACE,ATN,β 3 AR and hypertension in patients with type 2 DM. Methods281 recruited Chinese subjects were divided into two groups according to the oral glucose tolerance test (OGTT): ① non diabetes group including normal and impaired glucose tolerance (NGT,IGT): 169 cases;② Type 2 diabetes mellitus (DM): 112 cases. The subjects were genotyped for the ACE gene,the ATN gene and the codon 64 of β 3 AR gene polymorphisms by applying polymerase chain reaction (PCR),PCR restriction fragment length polymorphisms screening with the use of endonuclease. ResultsOur study found that the frequency of D/D genotype and D allele of ACE gene,a/a genotype and an allele of ATN gene in HT patients without DM were increased (P all <0.05);that the frequency of codon 64 mutation of β 3 AR gene also increased in HT patients with NGT (P < 0.05 ). In the model of multiple factors non condition al Logistic regression analyses,HT had relationship with history of hypertension,age and glucose tolerance (OR=10.745 7,1.780 4, 2.034 6;P=0.000 4, 0.000 0 ,0.024 6;respectively),with polymorphism of ATN gene,β 3AR gene,ACE gene (OR= 2.273 6 ,1.935 3,1.830 9;P=0.054 3,0.028 7,0.043 2;resceptively). ConclusionThese results suggest that variants of ACE gene,β 3AR gene,ATN gene were associated with HT in type 2 DM.

Intensive Antihypertensive Treatment with Angiotensin Receptor Blocker Combined with Hydrocholorthiazide Reduces Urinary Angiotensinogen in Patients with Type 2 Diabetes Mellitus

Purpose: Local activation of rennin-angiotensin system (RAS) is involved in the progression of chronic kidney disease (CKD). One of the RAS components, angiotensinogen (AGT) has been known to be a potential surrogate biomarker for the renal RAS activity. Measuring the daily urinary excretion of AGT (U-AGT), the present study addressed whether the intensive blood pressure (BP) lowering with combined antihypertensive agents could improve such an abnormality in diabetic CKD patients. Methods: Uncontrolled hypertensive patients with type 2 diabetes with mild to moderate nephropathy previously receiving angiotensin receptor blockers (ARB) in an optimal dose alone were recruited for a better blood pressure (BP) control. Urinary specimens were subjected to a quantitative measurement of a daily urinary protein (U-prot) and U-AGT. After the baseline measurement, intensive antihypertensive therapy was attempted by switching the ARB dose to a fixed combination formula of candesartan 8 mg plus hydrochlorthiazide (HCTZ) 6.25 mg and the patients were followed up for 24 weeks. Comparison of parameters was then made between the values at the baseline and the end of the study. Results: At baseline, there was a significant positive correlation between U-AGT and U-prot, and between U-AGT and serum creatinine (Cr) concentration. In addition, U-AGT was inversely correlated with estimated glomerular filtration rate (e-GFR). Switching the antihypertensive regime from ARB alone to the combined ARB/HCTZ significantly reduced BP, U-AGT and U-prot. The magnitude of the reduction in U-prot was positively correlated with that in U-AGT. A stepwise regression analysis showed that HbA1c, e-GFR and the reduction in U-prot in response to the intensive antihypertensive therapy were positively correlated with the reduction in U-AGT. Conclusion: U-AGT is increased and positively correlated with U-prot in patients with type 2 diabetic nephropathy. Intensive antihypertensive treatment with ARB combined with HCTZ reduces both U-AGT and U-prot, presumably via an amelioration of an accelerated renal RAS activity. These data also suggest that U-AGT can be used as a potential therapeutic surrogate biomarker for the activated renal RAS in patients with diabetic nephropathy.

Influence of electroacupuncture with acupoints selected along meridians on gene expression of angiotensinogen of myocardial ischemia rats

Objective:To observe the effects of electroacupuncture along meridians on the expression of angiotensinogen(AGT)mRNA in myocardial tissue of myocardial ischemia(MI)rats.Methods:SD rats were randomly divided into four groups:control group,MI model group,Neiguan(PC6)point group(EA group)and non-acupoint(the lateral-superior side of the hip)group.Myocardial infarction was produced in rats with 85 mg/kg of isoproterenol administered subcutaneously twice at an interval of 24 h.Rats of EA group and non-acupoint group were treated with electroacupuncture,once daily for five consecutive days.Gene chip was used to detect RAS-related genes of myocardial tissue from the model group and the EA group.Cardiac index and pathological staining were observed of four groups.Real-time quantitative fluorescent PCR was used to detect the expression of AGT mRNA in cardiac tissue.Results:The expression of RAS-related genes were different between the model group and the EA group.The difference of AGT mRNA was the most significant.The cardiac index and AGT mRNA expression in the model group were significantly higher than those in the control group(P<0.01).While those in the EA group were significantly lower than model group(P<0.05).The cardiac index and the expressions of AGT mRNA in the nonacupoint group were significantly higher than those in the EA group(P<0.01),and there was no difference with the model group.Conclusion:Electroacupuncture along meridians can improve myocardial ischemia in rats,and its mechanism may be related to the down-regulation of AGT mRNA expression in myocardial tissue.

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive response.We previously reported that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p and rs699 A>G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq.The AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT transcription.The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related phenotypes.Methods We used in silico,in vitro,in vivo,and retrospective models to test this hypothesis.Results In silico,rs699 A>G is predicted to increase miR-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA-binding site in the AGT mRNA.Unexpectedly,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model.Genotype-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>T.However,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mRNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with HTN.Conclusions We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White participants.Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>G.Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Effect of Electroacupuncture Stimulation on mRNA Expression of Angiotensinogen,Angiotensin Ⅱ Type 1 Receptor,Endothelin-1,and Endothelin A Receptor in Spontaneously Hypertensive Rat Aorta

Objective： To observe the effect of electroacupuncture （EA） stimulation on the expressions of angiotensinogen （AGT）, angJotensin Ⅱ type 1 receptor （ATIR）, endothelin-1 （ET1）, and endothelin A receptor （ETAR） mRNA in spontaneously hypertensive rat （SHR） aorta. Methods： Eighteen male SHRs were randomly divided into three groups, an SHR group, an SHR Baihui （DU 20） and Zusanli （ST 36） acupoint （SHR-AP） group, and an SHR non-acupoJnt （SHR-NAP） group, with 6 rats in each group. Six Wistar rats were used as a control. Rats in the SHR-AP group were stimulated by DU 20 and ST 36 acupoints, both of which were connected with EA. EA was handled one time every Monday, Wednesday and Friday, for total 24 times （8 weeks）. SHR- NAP rats were acupointed at a 15° angle flat into 0.5 cm to two points, which were 1 and 2 cm from rail tip separately. EA parameters were the same as the SHR-AP rats. SHR control rats and Wistar rats were fixed without EA. Real-time quantitative polymerase chain reaction （PCR） was used to measure AGT, AT1 R, ET1, and E-TAR mRNA expression in rat aorta. Results： EA stimulation significantly reduced rat aorta vascular AGT, ET1, ETAR and AT1R mRNA expressions in the SHR-AP and SHR-NAP groups （P〈0.01）. Among these four genes, ATIR mRNA expression was significantly lower in the SHR-AP than in the SHR-NAP group （P〈0.01）. Conclusion： EA could reduce the ATIR mRNA expression in SHR-AP rat aorta, indicating a potential mechanism for the hypotensive effects of EA.

Research progress of the relationship between angiotensinogen gene polymorphisms and coronary heart disease

Coronary heart disease （CHD） is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly that CHD is determined by a complex interplay of genetic and environmental factors. Many clinical data have showed that the renin-angiotensin system （RAS） hypertension and CHD involved in many cardiovascular diseases, such as Angiotensinogen （AGT） is the key components of the RAS system, and two gene polymorphisms of AGT had been detected of the CHD risk： M235T and T174M. This article reviews the effects of AGT gene polymorphisms on the CHD.

Relationship between angiotensinogen gene M235 Tvariant with diabeticnephropathy in Chinese N I D D M

Objective To investigate whether angiotensinogen (AGT) gene M235T variant is associated with non insulin dependent diabetes mellitus without nephropathy (DN -), and diabetic nephropathy (DN +) in Chinese non insulin dependent diabetes mellitus (NIDDM) Methods The subjects in DN + group, DN - group and control group were well matched with sex, age and duration of disease, and the two case groups were divided into two subgroups as with and without hypertension respectively The M235T polymorphism of AGT gene of 84 cases with DN -, 96 patients with DN + and 98 controls were determined by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) analysis of the region of the variant, i e M235T polymorphism Results The increased frequencies of T allele (0 82) and TT genotype (0 70) were observed in 96 subjects with DN + as compared with 98 control subjects (0 63 and 0 43, respectively, P =0 003, P =0 0004) The odds ratio associated with TT genotype was 3 47 (95%CI: 1 51-7 94; P =0 0033) for diabetic nephropathy in analysis adjusted for several risk factors of diabetic nephropathy, such as body mass index, systolic and diastolic blood pressure, serum cholesterol, low density lipoprotein and high density lipoprotein Subgroup analysis of the 67 patients in DN + group with hypertension revealed similar distributions of M235T genotypes and alleles to those in the DN + without hypertension subgroup There was no difference in allele and genotype distribution between 84 DN - patients and the controls Similarly, frequencies of the AGT M235T genotype and allele were not different between two DN - subgroups Conclusions AGT gene M235T polymorphism is associated with diabetic nephropathy in NIDDM TT genotype of the AGT gene might be an independent risk factor of diabetic nephropathy in Chinese NIDDM patients

AGT-M235T及eNOS-T786C基因多态性与急性心肌梗死的相关研究

目的探讨血管紧张素原(AGT)-M235T、内皮型一氧化氮合酶(eNOS)-T786C基因多态性与急性心肌梗死(AMI)的相关性。方法选取2021年7月至2023年7月在玉林市中医医院就诊的AMI患者200例作为AMI组,同期体检健康者200名作为对照组,比较两组的基因型及等位基因频数的差异。结果AMI组男女间的eNOS-T786C基因型及等位基因频数比较,差异有统计学意义(P<0.05);对照组男女间的AGTM235T基因型、AGT-M235T等位基因及eNOS-T786C基因型频数比较,差异有统计学意义(P<0.05)。两组女性的eNOS-T786C基因型及等位基因频数比较,差异有统计学意义(P<0.05)。分别以GG和TT基因型作为参照进行二元logistic回归分析,结果表明AA及CC基因型可能是AMI患病的危险因素(AA:OR=2.281,P<0.05;CC:OR=2.934,P<0.05),而GA基因型可能是AMI患病的保护因素(OR=0.803,P<0.05)。结论AGT-M235T的AA基因型及eNOS-T786C的CC基因型与AMI易感性密切相关,临床需要重视AMI患者相关基因型的危险因素及保护因素。

Molecular mechanism of Radix astragali on improvement of insulin sensitivity of SD rats treated with low dose dexamethasone

Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats （6 per group） received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose （10 g material/kg） of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC）, high density lipoprotein cholesterol （HDLC）, glucose （GLU） and insulin （INS） levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index （QUICKI） than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.

肾素基因G10631A和血管紧张素原基因C521T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C521T多态性与脑梗死的关系。方法采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测82例脑梗死患者和89名正常对照者的REN基因10631位点、AGT基因521位点的多态性,并用Logistic回归分析两基因多态性与脑梗死的关系。观察两组基因单倍型的分布。结果脑梗死组REN基因10631 AA基因型(31.7%)、A等位基因(49.4%),AGT基因521TT基因型(22.0%)、T等位基因频率(28.0%)显著高于正常对照组(10.1%、30.3%、6.7%、11.8%)(均P<0.05)。Logistic回归分析显示,REN基因10631AA基因型、AGT基因521TT基因型增加脑梗死的发生概率,发病的相对危险度(OR)分别为2.798、3.492(均P<0.05)。脑梗死组基因单倍型521T-10631A的分布频率明显高于正常对照组(P<0.005)。结论 REN基因10631AA基因型和A等位基因、AGT基因521TT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可能是脑梗死发病的遗传危险因素。

血管紧张素原基因多态位点AGT174与原发性高血压相关性的研究

本文采用ＰＣＲ、限制性酶切和电泳分型等方法，分别对９０例原发性高血压患者和１０９例正常人血管紧张素原基因多态位点ＡＧＴ１７４进行了检测，结果表明，高血压组中三种基因型的分布与对照组显著不同，提示该位点变异与原发性高血压的发生相关。

血管紧张素原在儿童过敏性紫癜肾炎发生发展中的作用

目的过敏性紫癜(HSP)是儿童最常见的血管炎,约50%的HSP患儿累及肾脏,部分甚至进展为终末肾,然而其发病机制尚不明确;近年来研究发现肾内肾素-血管紧张素系统(RAS)可能参与紫癜性肾炎(HSPN)的发病。该研究拟探讨血管紧张素原(AGT)与儿童HSP肾损伤的相关性。方法选取30个HSPN患儿、31个HSP患儿及25个正常对照儿童。收集治疗前患儿及对照组的血液和新鲜晨尿,检测血清尿素氮(BUN)、肌酐(SCr)、肾小球滤过率(e GFR)、尿蛋白(UP)、尿肌酐(UCr)等指标,用人AGT ELISA试剂盒测定血清及尿液中的AGT含量。结果 HSPN组患儿尿血管紧张素原/尿肌酐(UAGT/UCr)水平高于HSP患儿及正常对照组儿童(P<0.05);HSP患儿UAGT/UCr水平与正常对照组儿童两组间差异无统计学意义(P>0.05)。3组血清AGT水平差异无统计学意义(P>0.05)。UAGT与BUN和血清AGT无相关,与SCr和UP/UCr呈正相关,与e GFR呈负相关。结论肾内RAS活化可能参与HSP患儿肾脏损害的发生发展,可以通过监测UAGT来判断疾病的严重程度,预测过敏性紫癜肾损伤的进展及预后。

原发性高血压患者血管紧张素原基因多态性及血浆NO、内皮素水平检测

目的:检测原发性高血压(EH)患者血管紧张素原(AGT)基因M235T、T174M多态性和血浆一氧化氮(nitricoxide,NO)、内皮素(ET)的水平。方法:对100例EH患者、40例正常血压对照组采用聚合酶链反应、限制性内切酶酶解及电泳分型的方法对AGT基因M235T、T174M多态性进行分析,硝酸还原酶法和放射免疫法分别测定2组血浆NO、ET水平。结果:①EH组中M235TT、T174TM、T174MM基因型频率及T174M等位基因频率显著高于对照组(P均<0.05)。②EH组与对照组比较血浆NO水平降低;ET水平升高(P<0.001)。③EH组中T174MM型血浆NO水平明显低于T174TM型和T174TT型(P均<0.001);而ET水平T174MM型和T174TM型明显高于T174TT型(P均<0.001);血浆NO、ET水平在M235T3种基因型之间差异无统计学意义(P>0.05)。结论:①T174MM基因型和T174M等位基因是EH发病的危险因素。②EH存在血管内皮舒缩功能障碍,表现为血浆NO水平降低、ET水平升高。