血管紧张素II1型受体基因多态性与原发性高血压的关系

目的探讨血管紧张素Ⅱ1型受体（AT1R）基因多态性与原发性高血压（EH）之间的关系。方法应用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）对200例汉族EH患者（EH组）和192例正常血压者（对照组）的ATlR基因1166A／C及-810A／T多态性进行检测,测定空腹血糖、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）及高密度脂蛋白胆固醇（HDL—C）等生物化学指标,分析各基因型和等位基因频率与EH的关系。结果1166A／C等位基因和基因型频率在EH组和对照组的分布无统计学差异（P均〉0．05）,-810A／T各基因型在EH组和对照组间差异有统计学意义（χ^2=10．862,P=0．004）,-810T等位基因频率在EH组显著增高[22．5％（102／400）与11．5％（44／384）,χ^2=12．745,P=0．000],用Logistic回归模型校正了传统危险因素的影响后,-810AT和TT基因型的携带者患高血压的危险性显著增加（P=0．003,OR值为2．57,95％CI：1．37～4．84）。结论AT1R-810A／T多态性与EH发病相关,-810T等位基因可能是EH发病的风险因子。     

Angiotensin I-converting enzyme gene polymorphism in a Serbian population: a gender-specific association with hypertension

Human essential hypertension has a multifactorial origin and is caused by a delicate interaction between susceptibility genes and environmental factors. Candidate genes are selected from the renin-angiotensin system (RAS) and are physiologically implicated in blood pressure regulation. We investigated the association between insertion/deletion (I/D) polymorphism at the angiotensin-converting enzyme ( ACE ) locus and hypertension in a case-control study conducted in a population of Caucasians (175 females, 210 males). Case subjects were those with untreated borderline hypertension. A significant, moderate, male, gender-specific independent association between DD genotype and high blood pressure was found. Adjusted odds ratio (OR) was 2.0 (95% CI, 1.1 to 3.9; p = 0.03) in the whole group and 2.5 (95% CI, 1.2 to 5.1; p = 0.01) in the group truncated on the basis of age ( &#104 50 years). Our findings support the hypothesis that ACE is a gender-specific candidate gene for hypertension.     

Angiotensin I-converting enzyme gene polymorphism in a Serbian population: a gender-specific association with hypertension

Human essential hypertension has a multifactorial origin and is caused by a delicate interaction between susceptibility genes and environmental factors. Candidate genes are selected from the renin-angiotensin system (RAS) and are physiologically implicated in blood pressure regulation. We investigated the association between insertion/deletion (I/D) polymorphism at the angiotensin-converting enzyme (ACE) locus and hypertension in a case-control study conducted in a population of Caucasians (175 females, 210 males). Case subjects were those with untreated borderline hypertension. A significant, moderate, male, gender-specific independent association between DD genotype and high blood pressure was found. Adjusted odds ratio (OR) was 2.0 (95% CI, 1.1 to 3.9; p=0.03) in the whole group and 2.5 (95% CI, 1.2 to 5.1; p=0.01) in the group truncated on the basis of age (< or = 50 years). Our findings support the hypothesis that ACE is a gender-specific candidate gene for hypertension.     

X-linked angiotensin II type 2 receptor gene polymorphism -1332A/G in male patients with essential hypertension

BACKGROUND: The role of AT2R in regulation of blood pressure (BP) was mainly investigated in animal models. It is proposed to be a negative regulator of BP. X-linked AT2R -1332 A/G polymorphism has been denoted as functional. This polymorphism was associated with certain cardiovascular phenotypes in hypertensive patients, but it was poorly investigated in essential hypertension. The aim of our study was to evaluate possible association of -1332 A/G gene polymorphism with essential hypertension in males from Serbian population. METHODS: The study group included 304 men of Caucasian origin, 190 normotensive (NT) and 114 hypertensive (HT), free of cardiovascular disorders. Genotyping was done by PCR RFLP method. RESULTS: G/- genotype was in association with HT (OR 1.6, CI=1.0-2.6, p=0.04). Stratification by age (<40 years, mean 31.65+/-5.29 and >40 years, mean 51.36+/-8.32) pronounced significance only in older males (OR 2.4, CI=1.2-5.0, p=0.02). After adjustment for confounding factors the OR for hypertension remained unchanged and significant (adjusted OR 2.3, CI=1.0-5.4, p=0.04). Conclusion: Hemizygosity for the G allele was found to be susceptibility factor for hypertension in males. Still, clarifying the role of AT2R in development of human hypertension requires further replication studies in larger and different populations.     

血管紧张素Ⅱ1型受体A1166C多态性与高血压左心室肥厚的相关性研究

目的 探讨血管紧张素Ⅱ1型受体（AT1R）A1166C多态性与高血压及高血压左心室肥厚的关系。方法 选取249例原发性高血压患者进行超声心动图检查和AT1RA1166C多态性测定。结果 AA基因型患者收缩压较AC＋CC基因型高，差异具有显著性（P=0．006）；舒张压具有同样趋势（P=0．342）。高血压人群中，AA基因型与AC＋CC基因型相比，左心室内径、室间隔厚度、左心室后壁厚度、左心室质量及左心室质量指数差异均无显著性（P〉0．05）。结论 中国原发性高血压人群中，AT1R基因A1166C多态性AA基因型可能与血压升高有关；可能与中国人群原发性高血压左心室肥厚无关。     

β肾上腺素能受体基因多态性与原发性高血压的关系

目的:β肾上腺素能受体包括β1,β2和β3三种亚型,分析其基因多态性与原发性高血压的关系。方法:试验于2003-02/2005-09在重庆医科大学生物医学工程研究室进行。选择在清华大学第一附属医院和重庆医科大学第二附属医院就诊和体检的150例原发性高血压患者,男80例,女70例,年龄(56.53±5.60)岁;130例正常对照者,男70例,女60例,年龄(55.62±8.63)岁,对试验均知情同意。测试受试者坐位血压。用聚合酶链反应-限制性片段长度多态性技术和等位基因特异性聚合酶链反应法分析β1-肾上腺素能受体的Ser49Gly和Arg389Gly,β2-肾上腺素能受体的Arg16Gly和Gln27Glu,β3-肾上腺素能受体的Trp64Arg基因多态性,并分析其基因多态性与原发性高血压的相关性。结果:①β1-389原发性高血压组和对照组的Arg/Arg,Arg/Gly和Gly/Gly基因型频率分别为:0.56,0.32,0.12和0.74,0.22,0.04(P<0.05),Arg和Gly的等位基因频率在原发性高血压组和对照组分别为0.72,0.28和0.85,0.15,两组间差异显著(P<0.05)(OR=0.45,95%可信区间:0.30-0.69)。②β2-16原发性高血压组和对照组的Arg/Arg,Arg/Gly和Gly/Gly基因型频率分别为:0.17,0.67,0.16和0.27,0.69,0.04(P<0.05)。Arg和Gly的等位基因频率在原发性高血压组和对照组分别为0.51,0.49和0.62,0.38,两组间差异显著(P<0.05)(OR=0.64,95%可信区间:0.46～0.90)。③β1-肾上腺素能受体的Ser49Gly,β2-肾上腺素能受体的Gln27Glu,β3-肾上腺素能受体的Trp64Arg的基因型频率和等位基因频率在原发性高血压组和对照组之间差异无显著性(P>0.05)。所有组的基因多态性分布均符合Hardy-Weinberg定律。结论:在所研究的中国人群中,β1-389Arg/Gly和β2-16Arg/Gly基因多态性与原发性高血压的发病有联系。     

中国汉族人血管紧张素Ⅱ1型受体基因A1166C多态性与原发性高血压关系的系统分析

目的　Meta分析中国汉族人血管紧张素Ⅱ1型受体基因A1166C多态性与原发性高血压的关系。方法　以原发性高血压组和健康对照组基因分布的OR值为统计量,全面检索相关文献并剔除不符合要求的文献。应用RevMan4. 2软件对各研究结果进行一致性检验和数据合并。结果　11篇文献的病例对照试验一致性较好。原发性高血压组1 121例,健康对照组1 114例,数据合并结果AA/(AC+CC)、(AC+CC) /AA及C/AOR值( 95%CI)分别为0. 52 ( 0. 40, 0. 67 ), 1. 93 ( 1. 49, 2. 50 ), 1. 92 ( 1. 52, 2. 43 ),均为P<0. 000 01。结论　中国汉族人A1166C基因多态性的AA基因型与原发性高血压呈负相关,AC+CC基因型与原发性高血压呈正相关,即1166A→C突变与原发性高血压有关。     

Influence of angiotensin II type 1 receptor polymorphism on hypertension in patients with hypercholesterolemia

Essential hypertension results from the combined influence of environmental and genetic factors. The relationship between angiotensin II type 1 receptor (AT(1)) A-C(1166) polymorphism and essential hypertension is controversial. Because it is accepted that high concentration of serum cholesterol is one of risk factors of atherosclerosis, we investigated the influence of the AT(1) A-C(1166) polymorphism on hypertension in patients with hypercholesterolemia. A total of 131 hypertensive, 97 borderline, and 175 normotensive subjects were enrolled in this study. We selected hypercholesterolemic subjects on the condition that their serum concentration of total cholesterol was >220 mg/dl, and obtained 55 hypertensive, 24 borderline, and 52 normotensive subjects with hypercholesterolemia. There were no significant differences in the genotype nor allele frequency between hypertensive and normotensive subjects in the overall population. However, the presence of the C allele of the AT(1) gene has a tendency to increase the value of systolic blood pressure not only in subjects with hypercholesterolemia but also in the overall population. Furthermore, we found a significant relationship between the AT(1) polymorphism and hypertension in subjects with hypercholesterolemia; i.e., the frequency of the C allele of the AT(1) gene was significantly higher in hypertensives than in normotensives (P<0.005). These results suggested that high concentration of total cholesterol was an important risk factor to the occurrence of essential hypertension for patients who carried the C allele of the AT(1) gene.     

Angiotensin II type 1 receptor blocker inhibits pulmonary injury

PURPOSE: Pulmonary damage and fibrosis may be the result of diverse forms of injury and there is an association between pulmonary diseases and cardiovascular events. The purpose of this study was to evaluate the effects of an angiotensin II type 1 receptor blocker, valsartan, on systemic, cellular, and fibrotic consequences of pulmonary injury induced by the anti-neoplastic antibiotic, bleomycin. METHODS: Sprague Dawly rats were used in the classical bleomycin model of pulmonary fibrosis. Bleomycin (1 unit, n = 7) was administered intra-tracheally to induce lung injury. Valsartan (0.66 mg) was given either concomitantly (n = 9) or for two days prior to bleomycin (n = 8). A control group (n = 6) was given normal saline. RESULTS: Valsartan-treated animals showed abrogation of weight loss, suppression of release of total and active transforming growth factor beta-1 (TGF-beta1), and diminished connective tissue synthesis. In an explant, lung tissue culture model devoid of alveolar macrophages (saline control, n = 3; bleomycin, n = 6; bleomycin plus valsartan, n = 12), both total and active TGF-beta1 were suppressed in the valsartan-treated cohort. CONCLUSIONS: Valsartan, known to have cardio-protective properties, was shown to be protective of bleomycin-induced pulmonary injury. Thus, ARBs may be beneficial in both cardiac and pulmonary diseases.     

原发性高血压和肾性高血压患者血管紧张素Ⅱ2型受体基因单核苷酸多态性的相关性研究

目的探讨原发性高血压和肾胜高血压患者血管紧张素Ⅱ2型受体基因A1675G单核苷酸多态性与高血压发生的关系。方法应用直接测序方法对80例原发性高血压、80例肾性高血压和40名正常人群中血管紧张素U2型受体基因作SNP分型。结果原发性高血压组A等位基因频率56．88％（91／160）,对照组30．00％（24／80）,差异有统计学意义（X^2=15．44,P〈0．001）;A等位基因频率与肾性高血压无关联E42．50％（68／160）与30．00％（24／80）,X^2=3．52,P〉0．05）。基因型分析原发性高血压和肾性高血压差异均无统计学意义（P均〉0．05）。结论血管紧张素Ⅱ2型受体基因的A1675G单核苷酸多态性与原发性高血压发病有关。与肾性高血压无关。     

CYP17A1基因多态性与原发性高血压的相关性研究

目的探讨CYP17A1基因rs11191548位点多态性与原发性高血压关系。方法选取原发性高血压患者143例和健康体检者199例。应用Taq Man探针分析CYP17A1基因rs11191548位点多态性的基因型,并探讨其相关性,采用逐步Logistic回归分析,分析获得性因素对高血压的影响。结果经χ~2检验,2组间基因型分布差异有统计学意义(P0.05),2组间等位基因频率分布差异有统计学意义(P0.05)。TT和CT基因型较CC基因型对于患病具有较高风险,CC基因型的个体患高血压的风险分别是携带TT基因型的0.370倍,携带T等位基因的个体患高血压的风险是携带C等位基因的1.776倍。获得性因素中,空腹血糖、甘油三酯及年龄较高的人群具有更高的患病风险。结论 CYP17A1基因rs11191548多态性与原发性高血压发病可能相关,其中TT基因型及T等位基因的个体患高血压的风险升高,获得性因素对高血压的发病有显著影响。     

短暂性脑缺血发作和原发性高血压与胰岛素受体基因多态性的关联

目的:观察胰岛素受体基因第17外显子基因多态性与中国人短暂性脑缺血发作和原发性高血压的关联。方法:选择2004-06/10在青岛大学医学院附属医院住院短暂性脑缺血发作患者75例,分为短暂性脑缺血发作组(30例)及原发性高血压+短暂性脑缺血发作组(45例),选取同时期性别年龄相当的68名健康查体者作为正常对照组。应用聚合酶链式反应、单链构象多态性分析的方法分析胰岛素受体基因17外显子变异的多态性分布情况。结果:143名被试者全部进入结果分析。①单链构象多态性分析显示两病例组与对照组均出现3种不同的DNA带型,分别称为Ⅰ,Ⅱ,Ⅲ带型。②带型分布频率:短暂性脑缺血发作组和原发性高血压+短暂性脑缺血发作组中带型Ⅱ出现频率高于对照组(64.35%,55.56%,31.35%,P<0.05);带型Ⅰ出现频率低于对照组(26.67%,26.68%,61.76%,P<0.05);带型Ⅲ3组间无差异。结论:①提示带型Ⅱ可能是短暂性脑缺血发作的易感基因标志,而带型Ⅰ可能是抗性基因标志。②胰岛素受体基因多态性可能是短暂性脑缺血发作的独立危险因素之一,且参与原发性高血压的发病。     

短暂性脑缺血发作和原发性高血压与胰岛素受体基因多态性的关联

目的：观察胰岛索受体基因第17外显子基因多态性与中国人短暂性脑缺血发作和原发性高血压的关联。方法：选择2004-06/10在青岛大学医学院附属医院住院短暂性脑缺血发作患者75例，分为短暂性腑缺血发作组（30例）及原发性高血压＋短暂性脑缺血发作组（45例），选取同时期性别年龄相当的68名健康查体者作为正常对照组。应用聚合酶链式反应、单链构象多态性分析的方法分析胰岛素受体基因17外显子变异的多态性分布情况。结果：143名被试者全部进入结果分析。①单链构象多态性分析显示两病例组与对照组均出现3种不同的DNA带型，分别称为Ⅰ，Ⅱ，Ⅲ带型。②带型分布频率：短新性脑缺血发作组和原发性高血压＋短暂性脑缺血发作组中带型Ⅱ出现频率高于对照组（64．35％，55．56％，31．35％，P〈0．05）；带型Ⅰ出现频率低于对照组（2667％，26．68％，61．76％，P〈0．05）；带型Ⅲ3组间无差异。结论：①提示带型Ⅱ可能是短暂性脑缺血发作的易感基因标志，而带型Ⅰ可能是抗性基因标志。②胰岛素受体基因多态性可能是短暂性脑缺血发作的独立危险因素之一，且参与原发性高血压的发病。     

Association of angiotensin II type 1 receptor gene polymorphism with carotid atherosclerosis.

BACKGROUND: Polymorphisms of the angiotensin II type 1 receptor (AGTR1) gene are associated with essential hypertension and cardiovascular disease, but the correlation between AGTR1 A1166C polymorphism and carotid intima-media thickness (IMT) remains unclear. We sought to demonstrate correlation between AGTR1 gene polymorphism and carotid atherosclerosis in a Chinese population. METHOD: A total of 150 patients diagnosed with essential hypertension were included in this study. The AGTR1 A1166C polymorphism was detected by restriction analysis of the polymerase chain reaction product with Ddel digestion. Carotid IMT was measured by B-mode ultrasonography. RESULTS: The AC genotype frequency and the C1166 allele frequency of the AGTR1 gene in essential hypertensive patients were significantly higher than in controls (22.00% vs. 6.00% for AC, p < 0.01; 18.67% vs. 8.00% for the C allele, p < 0.05). Hypertensive subjects with the AC genotype had increased carotid artery IMT and IMT/D (common carotid artery diameter) ratio compared with the AA genotype (IMT 1.14 +/- 0.39 vs. 0.88 +/- 0.16, p < 0.05; IMT/D 14.08 +/- 2.88 vs. 10.51 +/- 1.94, p < 0.01). CONCLUSION: These results suggest that the AGTR1 A1166C polymorphism is associated with essential hypertension and carotid atherosclerosis in a Chinese population.     

脂联素受体基因多态性与新疆维吾尔族、汉族原发性高血压的相关研究

目的:探讨脂联素受体基因rs12045862T/C、rs7539542G/C两个等位基因多态性与新疆维吾尔族、汉族原发性高血压之间的关系.方法:选择新疆维吾尔族原发性高血压患者309例,汉族原发性高血压患者368例,同时选取维吾尔族正常对照组300例,汉族正常对照组349例,采用TaqMan探针法,对脂联素受体基因的2个等位基因多态性rs12045862T/C、rs7539542G/C进行检测.结果:新疆维吾尔族、汉族原发性高血压组与正常对照组中脂联素受体基因rs12045862T/C基因多态性无显著差异(P=0.49;P=0.79),新疆维吾尔族、汉族原发性高血压组与正常对照组中脂联素受体基因rs7539542G/C基因多态性无显著性差异(P=0.18;P=0.55).结论:脂联素受体基因rs12045862T/C、rs7539542G/C等位基因多态性与新疆维吾尔族、汉族原发性高血压均无显著相关,其结论在两个民族中一致.     

Angiotensin II receptor antagonists in the treatment of hypertension.

The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) includes recommendations for the assessment of overall cardiovascular risk and the need for active antihypertensive drug therapy. Once the decision to initiate antihypertensive drug therapy has been made, JNC-VI recommends one of three paths for the choice of initial therapy: one path for patients with uncomplicated hypertension, another for those with well-defined indications for certain drugs and a third path for patients with various concomitant conditions in which one or another drug has favorable effects. At this time, the place for the newest class of antihypertensive drugs, the angiotensin II receptor antagonists, remains uncertain. Currently, they are considered reasonable alternatives for patients who have a compelling need for an angiotensin-converting enzyme (ACE) inhibitor but develop a cough while taking this medication. When data from ongoing trials become available, angiotensin II receptor antagonists may prove to be a good choice for initial therapy in many patients because of the favorable side effect profile of this class of drugs.     

E选择素基因多态性与蒙古族、汉族原发性高血压的病例对照研究

目的 高血压是由遗传和环境因素共同作用而引发的多因素疾病,它是常见的心血管疾病,同时也是中风和缺血性心脏病的重要危险因素,本研究预探讨E选择素(SELE)基因在蒙古族、汉族原发性高血压中的作用.方法 采用病例—对照研究和标签SNP(tagSNP)方法采集内蒙古自治区锡林郭勒盟蒙古族标本429例,汉族标本416例作为研究对象,采用高温连接酶检测反应进行基因分型并构建单体型.结果 SELE基因共挑选9个tagSNP位点,在汉族人群中,SELE基因rs3917458和rs2179172位点等位基因频率在高血压组和正常血压组间差异有统计学意义,其余位点的等位基因频率和基因型频率在两民族高血压和正常血压组间的分布均差异无统计学意义.单体型分析显示:在蒙古族人群,单体型GGC的频率在高血压组和正常血压组之间差异有统计学意义,在汉族人群中,单体型ACA和单体型TCC频率在高血压组和正常血压组之间差异均有统计学意义.结论 SELE基因rs2179172和rs3917458位点在汉族高血压组和正常血压组间有差异;携带单体型GGC的蒙古族个体形成高血压的风险增加,携带单体型ACA的汉族个体形成高血压的风险降低,而携带单体型TCC的汉族个体形成高血压的风险会增加.     

Angiotensin II type 1 receptor blockade: a new development in cardiovascular pharmacology

The renin-angiotensin-aldosterone system (RAS) plays a central role in blood pressure regulation and fluid and electrolyte homoeostasis. Blockade of this system with inhibitors of angiotensin-converting enzyme (ACE) has been shown to benefit several groups of patients, including those with essential hypertension, congestive heart failure, and post myocardial infarction. Inhibition of ACE also slows the progression of diabetic renal disease and diabetic retinopathy. The recent development of agents that are specific antagonists of angiotensin II (AII) has allowed us to block the RAS at receptor level. Inhibition of angiotensin II receptors has been shown to reduce blood pressure in hypertensive patients, without the side-effect profile of ACE inhibitors. It has yet to be shown whether manipulating the RAS in this way will confer the same morbidity and mortality benefits as those seen with ACE inhibition. Ongoing research will reveal whether All antagonists are beneficial in congestive heart failure, ischaemic heart disease and diabetes mellitus. The development of this new class of agent provides an exciting opportunity for clinicians to increase their understanding of the role of the RAS in health and disease.