血管紧张素转换酶基因多态性与非杓型高血压的关系

目的研究血管紧张素转换酶 ( ACE)基因插入 /缺失 ( I/ D)多态性与非杓型高血压 ( EH)的关系。方法　 1应用聚合酶链反应 ( PCR)方法扩增 5 0例正常人、99例高血压患者的 ACE基因上 2 87bp片段 ,根据插入 ( I)或 /缺失( D)来判断其多态性。 2高血压患者行 2 4h动态血压监测 ( ABPM) ,根据 ABPM结果分为杓型 EH组和非杓型 EH组。结果　 1非杓型组与健康对照组相比 ,其 D等位基因及 DD基因型显著升高。 2非杓型组与杓型组相比 ,其 D等位基因及 DD基因型显著升高。3杓型组与健康对照组相比 ,ACE基因型和等位基因频率无显著性差异。结论　ACE基因多态性与非杓型高血压有关联性 ,DD基因型提示可能与高血压昼夜节律改变有关     

Relationship between angiotensin-converting enzyme gene polymorphism and insulin resistance in never-treated hypertensive patients

The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.     

原发性高血压血管紧张素转换酶基因多态性与性别的关系

目的　研究血管紧张素转换酶 (ACE)基因插入 缺失 (I D)多态性与不同性别原发性高血压 (EH)的关系。方法　应用聚合酶链反应技术分析 138例原发性高血压患者及 6 0名正常对照组的ACE基因型。结果　原发性高血压组缺失纯合子 (DD)基因型及D等位基因频率显著高于对照组 (P<0 .0 5 )。且男女两性相比 ,原发性高血压组男性DD基因型频率显著高于女性 (P <0 .0 5 ) ,收缩压水平亦显著高于女性 (P <0 .0 5 )。结论　原发性高血压与ACE基因I D多态性之间存在一种特殊的伴性关系。     

血管紧张素转换酶基因多态性与冠脉病变严重程度的相关性研究

目的探讨血管紧张素转换酶(ACE)基因I/D多态性与冠心病及冠脉病变严重程度的关系.方法对122例冠心病患者进行冠状动脉造影,判定冠脉病变支数(狭窄程度≥75%)和危险记分.用聚合酶链式反应(PCR)技术检测病例组和80例健康人群ACE基因多态性.结果ACE基因型分布和等位基因频率在病例组和对照组间差异有显著性,病例组DD基因型(38.5%)和D等位基因频率(55%)显著高于对照组(13.7%,41%;P＜0.05).冠脉病变支数和危险记分在ACE基因型间差异无显著性(P＞0.05).结论ACE基因多态性中DD型和D等位基因是冠心病发病的独立危险因素,但与冠脉病变严重程度不相关.     

Renal response to angiotensin-converting enzyme inhibition

Angiotensin-converting enzyme inhibitors, both teprotide and captopril, induce a potentiated renal vascular response in patients with essential hypertension, and with that a consistent increase in sodium excretion and occasionally an increase in glomerular filtration rate. In patients with advanced congestive heart failure resistant to other vasodilators, a similar triad occurs. It is not yet clear in which settings the renal response to angiotensin-converting enzyme inhibition reflects a reduction in angiotensin II formation—thus implicating the renin-angiotensin system in the pathogenesis—or an additional action, such as a potentiation of the local actions of bradykinin or enhanced prostaglandin formation. Under some circumstances, especially where a qualitatively and quantitatively similar response occurs to angiotensin antagonists and angiotensin-converting enzyme inhibitors or where an angiotensin antagonist prevents an additional response to a converting enzyme inhibitor, it is clear that the specific action of the converting enzyme inhibitor on angiotensin II formation is responsible. Unfortunately, for most responses in animal models and all responses in patients, such rigorous evidence is not yet available.     

原发性高血压患者血管紧张素转化酶基因多态性与血管内皮损伤的相关性

目的:探讨原发性高血压(EH)患者血管紧张素转化酶(ACE)基因I/D多态性与血管内皮损伤的相关性。方法:选择初次诊断的EH患者68例,采用聚合酶链反应(PCR)方法进行ACE基因分型,并测定其血浆可溶性P选择素(sP-selectin)、血栓烷B2(TxB2)和6-酮-前列腺素F1α(6-keto-PGF1α)浓度和血管假性血友病因子(v WF)抗原水平。结果:根据等位基因分布,EH患者分为DD型(18例)、ID型(26例)和II型(24例)3组;DD型的血浆sP-selectin、TxB2浓度和v WF抗原水平明显高于其他2型(P<0·05),而6-keto-PGF1α浓度则是DD型最低(P<0·05)。多因素Logistic回归分析显示ACE/DD基因型是引起患者血浆sP-selectin、TxB2、v WF升高和6-keto-PGF1α降低的独立危险因子。结论:ACE/DD基因型的EH患者较ACE/ID型和ACE/II型具有更为明显的血管内皮损伤倾向。     

新疆地区汉族血管紧张素转换酶基因多态性与冠心病相关性研究

目的 探讨新疆地区汉族人群血管紧张素转换酶(ACE)基因多态性与冠心病关联性.方法 应用聚合酶链反应(PCR)限制性内切酶方法检测了新疆地区汉族42例冠心病人和82例正常人群ACE基因多态性.结果 汉族正常人群的ACE基因三种基因型频率分别为:DD型19.51%,ID型32.93%,II型47.56%.D和I等位基因频率分别为36.0%和 64.0%;冠心病人的ACE基因三种基因型频率分别为:DD型28.57%,ID型30.95%,II型 40.48%.D和I等位基因频率分别为 44.05%和 55.95%,无显著性差异(χ2=1.996 8,P＞0.05),且男女之间也无显著性差异.结论 ACE基因多态性与新疆地区汉族冠心病关联性不大,但值得关注.     

T1198C polymorphism of the angiotensinogen gene and antihypertensive response to angiotensin-converting enzyme inhibitors.

This study examined the association between T1198C polymorphism of the angiotensinogen (AGT) gene and the blood pressure response to ACE inhibitors in a Chinese hypertensive cohort. After a 2-week single-blind placebo run-in period, benazepril (10-20 mg/day) or imidapril (5-10 mg/day) was administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphism, and the patients were classified as having the TT, TC, or CC genotype. The achieved changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed to determine their association with genotypes at the AGT gene locus. In the total 509 patients, the TT genotype was observed in 44 patients (8.7%), the TC genotype in 214 patients (42.0%), and the CC genotype in 251 patients (49.3%). The SBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -15.3+/-12.7 mmHg, -14.0+/-12.7 mmHg, and -14.4+/-12.4 mmHg, respectively (p=0.809). The DBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -8.5+/-8.1 mmHg, -8.3+/-7.5 mmHg, and -8.9+/-6.6 mmHg, respectively (p=0.638). There were no significant differences in the changes in SBP or DBP after treatment among the three genotype groups. In conclusion, these results suggest that the AGT genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibitors in Chinese hypertensive patients.     

原发性高血压代谢综合征与血管紧张素转换酶基因插入/缺失多态性关系的探讨

目的 :探讨原发性高血压 (EH)代谢综合征与血管紧张素转换酶 (ACE)基因插入 /缺失多态性的关系。方法 :选取EH患者 2 0 2例 ,其中男 116例 ,女 86例 ,年龄 30～ 72 (5 9.5 4± 9.2 6 )岁。符合代谢综合征者 10 6例 ,非代谢综合征 96例。应用聚合酶链反应 (PCR)测定两组ACE基因插入 /缺失多态性。结果 :EH代谢综合征组与非代谢综合征组ACE基因DD、ID、II基因型间无显著相关性 (χ2 =2 .5 4 5 ,P 0 .0 5 )。代谢综合征组ACE多态性基因型与腰围、高密度脂蛋白胆固醇 (HDL C)密切相关 (P <0 .0 1) ;与腰围 /臀围、三酰甘油 (TG)密切相关 (P <0 .0 5 ) ;与血压、血糖、胰岛素无关 (P 0 .0 5 )。代谢综合征组ACE基因DD、ID基因型腰围较II基因型显著增加 (P <0 .0 1,<0 .0 5 ) ;DD基因型腰围 /臀围、TG较II基因型显著增加 (P <0 .0 5 ) ;ACE基因DD基因型HDL C较II基因型显著降低 (P <0 .0 5 ) ;ACE基因DD、ID、II基因型间血压、血糖、胰岛素差异无统计学意义 (P 0 .0 5 )。结论 :EH代谢综合征与ACE基因多态性无显著相关性。但是代谢综合征患者肥胖、脂代谢紊乱与ACE基因多态性密切相关 ,而血压水平、胰岛素敏感性却与ACE基因多态性无关。     

Plasma aldosterone concentrations are not related to the degree of angiotensin-converting enzyme inhibition in essential hypertensive patients.

There is increasing evidence of important cardiovascular effects of aldosterone via classical mineralocorticoid receptors in the heart. Aldosterone plus excess salt administration has been shown to produce both cardiac hypertrophy and cardiac fibrosis in rats. Various clinical studies have reported that aldosterone plays an important role in cardiac hypertrophy; however, the factors that control plasma aldosterone concentrations during angiotensin-converting enzyme (ACE) inhibitor treatment have still not been established. In the present study, we examined the relationship between plasma aldosterone concentrations and the degree of ACE inhibition in 25 essential hypertensive patients treated with an ACE inhibitor. Blood pressure decreased with treatment and plasma ACE activity, estimated in vitro (by a colorimetric method) and in vivo (by plasma angiotensin II/angiotensin I ratio) assay, was suppressed compared with that of hypertensive patients treated with medication other than ACE inhibitors. No relationship was found between the level of ACE inhibition and plasma aldosterone concentrations, which rose in parallel with the duration of ACE inhibitor treatment. The present study demonstrates that continuous ACE inhibitor therapy produces significant suppression of plasma ACE activity in essential hypertensive patients, but that no relationship exists between plasma aldosterone concentrations and levels of ACE inhibition. Plasma aldosterone concentrations tend to increase with the duration of ACE inhibitor treatment, although this increase did not reflect a reduced inhibition of ACE activity.     

Association between a polymorphism in the angiotensin-converting enzyme gene and microvascular complications in Japanese patients with NIDDM

Summary The relationship between diabetic nephropathy and an insertion (I)/deletion (D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is still under debate. The association of ACE gene polymorphism with nephropathy and retinopathy was therefore examined in 362 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and 105 healthy control subjects. Distribution of the ACE genotype did not differ between healthy control subjects and diabetic patients without complications. However, the frequency of the D allele was significantly higher in the diabetic subjects with nephropathy than in those without (0.32 in normoalbuminuric patients vs 0.44 in albuminuria patients with albuminuria) (²=7.7; p=0.006). There was no significant association between ACE genotype and retinopathy. These observations thus demonstrate a significant association of the ACE gene polymorphism with nephropathy, but not with retinopathy, in Japanese patients with NIDDM.Abbreviations ACE Angiotensin-converting enzyme - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - UAI urinary albumin index - PCR polymerase chain reaction     

High frequency of DD polymorphism of the angiotensin-converting enzyme gene in Turkish asthmatic patients.

The aim of this study is to detect the incidence of the angiotensin-converting enzyme (ACE) gene polymorphism in Turkish asthmatic patients and to examine whether there is an association between the disease and ACE gene polymorphism. In our study, the genomic DNA of 100 asthmatic patients and 88 healthy subjects was analyzed Genomic DNA was isolated from peripheral blood by using standard methods. The intron 16 of the ACE gene was amplified by the polymerase chain reaction (PCR) method using primers ACE and ACEX to examine the presence and absence of a 287-base pair (bp) DNA fragment that showed I/D polymorphism genotypes. PCR products were separated by agarose gel electrophoresis and were visualized by a charge-coupled device camera. Serum ACE activities were measured using an ACE kit. The results were evaluated statistically using the chi-square test and one-way analysis of variance. Although the population of patients with asthma was characterized by a higher frequency (30%) of the DD genotype of ACE, they were characterized by lower frequency (48%) of the ID genotype of ACE (DD, 16%, and ID, 64%, in healthy control subjects). The frequency of the I and D alleles of the ACE gene was not significantly different between asthmatic patients (0.46/0.54) and healthy controls (0.52/ 0.48). In addition, in both asthmatic patients and controls, there was a significant decrease of the levels of ACE activity in individuals that have II genotypes when compared with individuals that have DD genotypes. ACE activities were increased significantly in all asthmatic patients (67.20 +/- 1.95 IU/L) compared with all healthy controls (60.90 +/- 2.12 IU/L).     

Relationship between polymorphism of angiotensin-converting enzyme 2 gene and the risk factor of essential hypertension with complicated stroke

Background Essential hypertension (EH) is considered to be one of the most important risk factor of ischemic stroke. Studies about risk factors in the patients are meaningful in early forecast and effective prevention of the onset of stroke. Renin-angiotensin-aldosterone system plays an important role in the regulation of blood pressure and the development of stroke, while recent studies have found that the angiotensin-converting enzyme 2 (ACE2) may be a reversal agent for the development and progression of ischemic stroke. Methods The ACE2 gene was measured in 139 EH patients with ischemic stroke using polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) tests. Detailed and complete clinical and biochemical data were collected, including pulse pressure, hsCRP, IMT, HDL-C and uric acid levels. Study the correlation between angiotensin-converting enzyme 2 gene and the risk factor for onset of ischemic stroke in EH patients. Results Pulse pressure, hsCRP, IMT and uric acid levels had a positive correlation with on- set of ischemic stroke in EH patients. Among male patients , pulse pressure, hsCRP, IMT and HDL-C were higher in patients carrying A allele than B allele (P < 0.05). While these factors were different in female pa- tients carrying different genotypes in which AA allele were highest. Patients with various genotypes showed different uric acid levels but showed no significant difference. Conclusion Among EH patients with complicated ischemic stroke, those carrying the A / AA allele show high level of risk factors and is likely to have the susceptibility of recurrence of stroke.     

Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure

OBJECTIVES: We evaluated the interaction of angiotensin-converting enzyme (ACE) inhibitor therapy with the effect of the ACE D/I polymorphism on heart failure survival. BACKGROUND: The ACE deletion allele, ACE-D, is associated with increased ACE activity. The utilization of ACE genotyping to predict the impact of ACE inhibitor dose has not been previously evaluated. METHODS: We prospectively studied 479 subjects with systolic dysfunction (left ventricular ejection fraction 0.25 +/- 0.08). Subjects were divided on the basis of ACE inhibitor therapy into low dose (50%, n = 201), or those receiving angiotensin receptor antagonists (n = 51). Patients were genotyped for the ACE D/I polymorphism, followed to the end point of death or cardiac transplantation, and transplant-free survival compared by genotype. RESULTS: The ACE-D allele was associated with an increased risk of events (p = 0.026). In analysis by ACE inhibitor dose, this effect was primarily in the low-dose group (1-year percent event-free survival: II/ID/DD = 86/77/71,2-year = 79/66/59, p = 0.032). In the standard-dose group, the impact was markedly diminished (1-year: II/ID/DD = 91/81/80, 2-year: 77/70/71, p = 0.64). The impact of beta-blockers and high dose ACE inhibitors was greatest in subjects with the ACE DD genotype (p = 0.001) and was less apparent with the II and ID genotypes (p = 0.38). CONCLUSIONS: Higher doses of ACE inhibitors diminished the impact of the ACE-D allele, and the benefits of beta-blockers and high-dose ACE inhibitors appeared maximal for DD patients. Determination of ACE genotype may help target therapy for patients with heart failure.     

Association between angiotensin-converting enzyme insertion/deletion polymorphism and treatment response in type 2 diabetic patients

BACKGROUND: Our objective was to determine whether the angiotensin-converting enzyme insertion-deletion (ACE I/D) polymorphism affects the treatment responses in type 2 diabetic patients. METHODS: A total of 117 type 2 diabetic patients with poor metabolic control were evaluated and their treatment intensified before re-evaluation after a mean follow-up of 16.0 months. New insulin treatment was started in 61% of patients, the majority of whom used a combination of insulin and tablets. Earlier insulin treatment was continued and intensified for 9% of patients, and 19% of patients used oral treatment only. As antihypertensive treatment, 34% of patients used diuretics, 27% ACE-inhibitors, 38% beta-blockers and 21% calcium-channel blockers during the follow-up. For dyslipidemia, 6% of patients used fibrates and none used statins. RESULTS: There was a decrease in glycohemoglobin A1 levels [-2.0 (0.3) (S.E.) %], plasma total cholesterol [-0.2 (0.1) mmol/l] and plasma triglycerides [-1.2 (0.4) mmol/l], and an increase in plasma HDL cholesterol [0.07 (0.02) mmol/l] and weight [2.1 (0.5) kg] in response to intensified treatment. The changes in glycohemoglobin A1 (GHbA1) levels and HDL cholesterol were significantly associated with the ACE I/D polymorphism. The patients with the ACE I/I genotype had a greater decrease [-3.0 (0.7)] in their GHbA1 levels than the patients with I/D [-2.1 (0.5)] or D/D [-1.8 (0.4)] genotypes (P<0.03). HDL cholesterol levels increased more among the subjects homozygous for the I allele [0.21 (0.05)] than the I/D [0.04 (0.03)] or D/D [0.04 (0.03)] subjects (P<0.03). CONCLUSIONS: The results suggest that the ACE I/D polymorphism is associated with treatment responses in type 2 diabetic patients.     

Intron-2 conversion polymorphism of the aldosterone synthase gene and the antihypertensive response to angiotensin-converting enzyme inhibitors

BACKGROUND: Aldosterone controls sodium balance and intravascular volume, and thus helps regulate blood pressure. Secretion of aldosterone is mainly regulated at the level of expression of the aldosterone synthase (CYP11B2) gene. The intron-2 conversion polymorphism of CYP11B2 was suggested to lead to overexpression of the gene, and may therefore have potential to predict the blood pressure response of patients with essential hypertension to angiotensin-converting enzyme inhibitors (ACEIs). OBJECTIVE: To investigate the association between the intron-2 conversion polymorphism and the blood pressure response to ACEIs in a hypertensive cohort. DESIGN AND METHODS: After a 2-week, single-blind, placebo run-in period, ACEIs were administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. The intron-2 conversion polymorphism was examined by polymerase chain reaction. RESULTS: The IwIw genotype was observed in 106 patients (20.8%), the IwIc genotype in 251 patients (49.3%), and the IcIc genotype in 152 patients (29.9%). After 6 weeks of treatment the reductions in diastolic blood pressure were significantly greater in patients carrying IcIc or IwIc compared with IwIw genotypes (9.2 +/- 7.2 or 9.2 +/- 7.1 versus 6.4 +/- 6.6 mmHg, respectively; analysis of variance, P = 0.001). Stepwise multiple regression analysis showed that significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P < 0.001), intron-2 conversion genotype (P = 0.006) and sex (P = 0.030). CONCLUSIONS: The intron-2 conversion polymorphism was related to the diastolic blood pressure lowering response in hypertensive patients treated with ACEIs. Interindividual variation in the efficacy of antihypertensive medications may therefore be influenced by genetic factors.     

自发性高血压大鼠心脏重构与ACE2 mRNA的表达

目的:观察不同月龄的自发性高血压大鼠(SHR)的心脏血管紧张素转换酶2(ACE2)mRNA表达水平,探讨心脏重构与ACE2的内在联系。方法:将12周龄雄性SHR 18只和12周龄WKY Wistar-Kyoto rats大鼠18只随机分为两组,从WKY大鼠组和SHR组中各抽取9只处死,剩余的9只再喂养12周后处死。测量大鼠心脏的质量(HW)与体质量(BW)并计算HW/BW的比值。以实时定量RT-PCR法检测ACE2 mRNA的表达。结果:①与同周龄WKY大鼠组比较,SHR组HW/BW的比值显著增加(P0.01);与12周龄SHR组比较,24周龄SHR组的HW/BW显著增加(P0.05)。②与同周龄的WKY大鼠组比较,SHR组ACE2 mRNA的表达显著降低(P0.01);与12周龄的SHR组比较,24周龄的SHR组ACE2 mRNA的表达显著降低(P0.01)。结论:自发性高血压大鼠心脏重构伴随着心脏中ACE2 mRNA的表达下调。     

Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and preeclampsia in Japanese patients

To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene ( ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen ( AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.061). Carrying the DD genotype may have some influence on the pathogenesis of preeclampsia, perhaps through effects on placental hypoxia or the interaction of hypertensive disease and atherosclerosis, although this influence may not be strong. Additional studies using a larger number of patients and analyses that include other genetic and environmental factors will be necessary to confirm these results.