糖尿病视网膜病变与血管紧张素转换酶基因缺失多态性的系统评价

采用meta分析系统评价中国汉族人血管紧张素转换酶(ACE)基因缺失(DD)多态性与2型糖尿病视网膜病变的关系.共纳入16篇符合条件的文献,共计2型糖尿病视网膜病变组1 014例,对照组1 135例.结果 显示OR为1.69(95%CI1.19～2.40),合并统计值Z=2.91(P=0.004).汉族人群ACE基因该多态性与糖尿病视网膜病变有关联,糖尿病视网膜病变组DD基因型增多.     

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。     

血管紧张素转换酶基因缺失多态性与冠状动脉病变

目的 :探讨血管紧张素转换酶 ( ACE)基因的插入 /缺失 ( insertion/deletion,I/D)多态性与冠状动脉病变的相关性。方法 :应用聚合酶链反应 ( PCR)扩增技术检测 86例行冠状动脉造影患者的 ACE基因 I/D多态性。结果 :冠状动脉异常组的 DD基因型频率 0 .41,D等位基因频率 0 .5 2 ,显著高于冠状动脉正常组的 0 .15和 0 .2 9( P <0 .0 5 ) ;DD基因型与冠状动脉病变有关 ( OR=3.97,P<0 .0 5 )。多支病变与 DD基因型的关系更为密切 ( OR=4.72 ,P<0 .0 5 )。冠状动脉正常组、单支病变组和多支病变组的 DD型频率依次为 0 .15、0 .33和 0 .46( P <0 .0 5 ) ,D等位基因频率为 0 .2 9、0 .44和 0 .5 6( P <0 .0 1)。结论 :ACE基因的 I/D多态性与冠状动脉病变及其严重程度相关 ,DD型及 D等位基因频率随冠状动脉病变及其程度的加重而逐渐升高。在冠状动脉病变患者中 DD及 ID型患者的吸烟率、甘油三酯及血压显著低于 型者 ( P <0 .0 5 ) ,说明 D等位基因及 DD基因型可能是冠心病低危人群冠状动脉病变的重要危险因素之一。     

广西地区汉族2型糖尿病血管并发症与血管紧张素转换酶Ⅰ基因多态性关系的研究

目的　探讨 2型糖尿病 (DM)及血管并发症与ACE基因插入 /缺失 (I/D)多态性的相关情况。方法　采用多聚酶链反应 (PCR)技术 ,对 12 0名广西地区汉族 2型DM组及 10 0名汉族正常对照组ACE基因I/D多态性进行检测。结果　 2型糖尿病肾病 (DN)组ACE基因D等位基因及DD基因型频率高于正常对照组 ,Ⅰ等位基因及Ⅱ基因型频率低于正常对照组 ;2型DM合并冠心病 (CHD)组ID基因型频率高于无CHD组 ,Ⅱ型基因频率低于无CHD组。 2型DM并视网膜病变 (DR)组ACE基因各等位基因及基因型频率与无DR组及正常对照组比较无统计学意义 ;2型DM并高血压组 (HP)ACE基因各等位基因及基因型频率与无HP组及正常对照组比较无统计学意义。结论　①广西地区汉族 2型DM合并DN及合并CHD与ACE基因I/D多态性有关 ;②DD基因型及D等位基因可能为 2型DM合并DN的易感基因 ,Ⅱ型及Ⅰ型等位基因可能为 2型DM合并DN的保护基因 ;ID型基因可能为 2型DM合并CHD的易感基因 ,Ⅱ型基因可能为 2型DM合并CHD的保护基因。③广西汉族 2型DM合并HP及合并DR与ACE基因I/D多态性无关联。     

胱抑素C、尿微量白蛋白肌酐比值与胱抑素C基因多态性老年糖尿病视网膜病变的相关性

目的考察胱抑素(Cys)-C、尿微量白蛋白肌酐比值(ACR)与Cys-C基因多态性老年糖尿病视网膜病变(DR)的相关性。方法 2型糖尿病(T2DM)患者126例按病变程度分为3组,即A(增殖期视网膜病变33例)、B(背景期视网膜病变50例)、C(无视网膜病变43例)3组。同期健康体检者32例为对照组。检测所有受试者Cys-C基因多态性、血糖、血脂、Cys-C和ACR。结果各组病程、空腹血糖(FBG)、糖化血红蛋白(HbA 1c)、总胆固醇(TC)、Cys-C和ACR差异有统计学意义(P0. 05),性别比、年龄、体重指数、血压、Cys-C基因分型差异无统计学意义(P0. 05)。各组Cys-C基因分型Cys-C和ACR差异无统计学意义(P0. 05),显著影响DR的因素分别为病程、Cys-C和FBG(P0. 05),Cys-C和ACR均与DR正相关(r=0. 791,P=0. 004;r=0. 598,P=0. 032)。结论血清Cys-C水平不受Cys-C基因多态性影响,血清Cys-C与ACR呈正相关,Cys-C与ACR可反映并预测老年DR的程度,可作为指示老年DR病变程度的危险因素。     

血管紧张素转换酶基因多态性与非胰岛素依赖型糖尿病伴微血管病变相关性的研究

目的　探讨血管紧张素转换酶 (ACE)基因多态性与非胰岛素依赖型糖尿病 (NIDDM )伴微血管病变的关系。方法　应用多聚酶链反应 (PCR)技术 ,对 15 1名NIDDM患者及 10 0名正常对照者的ACE基因插入 /缺失 (I/D)型多态性进行检测。结果　NIDDM患者DD型的发生频率明显高于正常人 (P <0 0 1) ;NIDDM伴糖尿病肾病者DD型发生频率明显高于无糖尿病肾病者 (P <0 0 5 ) ;NIDDM伴糖尿病眼底病变者DD型发生频率明显高于无糖尿病眼底病变者 (P <0 0 5 )。     

醛糖还原酶基因启动子区C-106T多态性与2型糖尿病患者视网膜病变易感性的研究

目的　研究中国北方汉族人 2型糖尿病视网膜病变 (DR)的易感性与醛糖还原酶 (AR)基因启动子区C 10 6T多态性的相关性 ,并探讨此多态性与AR基因 5′端 (AC)n多态性的连锁关系。　方法　 2型糖尿病 (T2DM)患者 116例 ,分为无微血管并发症 (NDC)组和糖尿病视网膜病变 (DR)组 ,提取外周血基因组DNA ,经PCR后用限制性内切酶BfαⅠ 5U进行酶切 ,酶切产物于 3 %琼脂糖凝胶电泳 ,用紫外凝胶成像系统GDS 76 0 0S观察结果。　结果　NDC组和DR组患者均发现 2种等位基因C T ,三种基因型CC、CT和TT ,CC基因型频率在DR组明显高于NDC组 ( 6 4.0 %vs 43.9%,P <0 .0 5 ) ,CT基因型频率在DR组明显低于NDC组 ( 30 %vs 5 4%,P <0 .0 1) ;Z - 2 C单倍型频率在DR组明显高于NDC组 ( 37.0 %vs 3 .0 %,P <0 .0 1) ,Z +2 C和Z +2 T单倍型频率在DR组明显低于NDP组 ( 11.0 %vs 42 .0 %,P <0 .0 1;2 .0 %vs 14.0 %,P <0 .0 5 )。　结论　CC基因型可能增加DR易感性 ,CT基因型可能减低DR易感性 ,且该多态性位点可能与AR基因 5′端 (AC)n多态性之间存在连锁不平衡。     

血管紧张素转换酶基因多态性与2型糖尿病并发高血压的相关性研究

目的 :研究血管紧张素转换酶 (ACE)基因多态性与 2型糖尿病并发高血压的关系。方法 :应用 PCR方法分析 149例 2型糖尿病患者及正常对照者的 ACE基因型。结果 :1ACE基因型及等位基因构成比 ,正常对照组与 2型糖尿病组无显著性差异 ;2并发高血压组 DD型及 D等位基因频率显著高于无高血压组 (P <0 .0 5 )。结论 :ACE基因 I/ D多态性与 2型糖尿病并发高血压有关。     

2型糖尿病肾病中ACE基因型和ACEI疗效关系的研究

目的探讨血管紧张素转换酶抑制剂(ACEI)治疗三种血管紧张素酶(ACE)基因型的2型糖尿病肾病的疗效有无差异,判断ACE基因插入/缺失(I/D)多态性对ACEI治疗2型糖尿病肾病的疗效有无预测作用.方法 68例2型糖尿病临床肾病患者,用胰岛素控制血糖,福辛普利20 mg/d治疗8周;用药前所有受试者以PCR方法检测ACE基因I/D多态性,并据其分为三组,ACE基因II型33例、ID型21例、DD型14例,于治疗前后分别测定血清ACE活性、尿白蛋白排泄率(UAE)、血清肌酐(SCr)、糖化血红蛋白(HbAlc)、体重指数(BMI)和平均动脉压(MAP).结果治疗前三组年龄、BMI、MAP、HbAlc、Scr、UAE差异均无显著性(P＞0.05),血清ACE活性在DD型组最高、ID组次之、II型组最低(P＜0.05);福辛普利治疗8周后,三组受试者BMI、Scr无明显变化,MAP、HbAlc均有下降,但三组间变化差异无显著性(P＞0.05);UAE、血清ACE活性下降的百分率在DD型组最高、ID型组次之、II型组最低,差异有显著性(P＜0.05);多因素相关分析UAE降低与MAP、HbAlc下降无相关,与血清ACE活性的下降相关(r=0.299,P＜0.05).结论 ACEI治疗2型糖尿病肾病疗效,在ACE基因DD型最好、ID型次之、II型最差,可能与其血清ACE活性的变化相关;检测ACE基因I/D多态性有助于预测ACEI治疗2型糖尿病肾病的疗效.     

血管紧张素转化酶抑制剂所致咳嗽与血管紧张素转化酶基因型相关性的研究

目的　探讨老年原发性高血压患者口服血管紧张素转换酶抑制剂 (ACEI )后发生咳嗽的机制。方法　应用聚合酶链反应 (PCR) ,检测老年原发性高血压患者口服ACEI后发生咳嗽与无咳嗽者的血管紧张素转化酶 (ACE)基因多态性 ,检测并比较两组患者血清ACE水平及ACE水平预测高血压患者口服ACEI引起咳嗽的敏感性和特异性。结果　ACEI所致咳嗽组ACE基因Ⅱ型的频率为4 0 % ,显著高于无咳嗽组 (2 0 % ,P <0 0 5 ) ,Ⅰ等位基因频率为 6 0 % ,显著高于无咳嗽组 (4 1% ,P <0 0 1)。两组患者血清ACE水平在DD型、ID型、Ⅱ型依次减低。咳嗽组血清ACE水平显著低于无咳嗽组 (P <0 0 0 1) ,血清ACE水平预测ACEI引起咳嗽的敏感性和特异性分别为 81%和 78%。结论　老年高血压患者口服ACEI所致咳嗽与血清ACE水平及ACE基因多态性有关。     

老年脑卒中患者血浆ACE水平及其基因多态性的研究

血管紧张素转换酶(ACE)在肾素-血管紧张素-醛固酮系统(RASS)和激肽释放内原-激肽系统(KKS)中发挥着重要的作用。近年研究发现,ACE通过不同的遗传机制在心脑血管疾病的发生发展中发挥作用,其多态性决定了血浆和细胞内ACE浓度,是研究各类心脑血管疾病遗传易感性的候选基因,本文通     

Dissociation between ACE activity and autonomic response to ACE inhibition in patients with heart failure

BACKGROUND: Administration of angiotensin-converting enzyme (ACE) inhibitors to patients with congestive heart failure has been shown to increase parasympathetic tone as indicated by increases in high-frequency heart rate variability. The mechanism for this effect, including its relation to changes in baroreflex activity, blood pressure variability, and suppression of ACE activity, remains undefined. This study was designed to test the relation of these variables, which may govern changes in autonomic activity, to the previously described increase in parasympathetic tone. METHODS: Seven patients with heart failure received a 3-hour infusion of the ACE inhibitor enalaprilat. Hemodynamic variables and parameters of heart rate and blood pressure variability, baroreflex gain derived from the interaction of heart rate and blood pressure variability, and serum ACE activity were measured during and after the infusion. Measures of heart rate and blood pressure variability were also compared against a historic control group. RESULTS: Serum ACE activity was significantly suppressed throughout and after enalaprilat infusion. Hemodynamic measures did not change other than a small decline in right atrial and pulmonary capillary wedge pressures. Parasympathetic tone showed an initial significant increase with a peak at 2 hours but then declined below baseline 8 hours after initiation of enalaprilat infusion. Sympathetically influenced low-frequency heart rate variability was significantly increased above baseline in the enalaprilat treatment group 8 hours after initiation of the infusion. Baroreflex gain showed a significant trend to an increase with the maximum value coinciding with the peak in parasympathetic tone. There was no change in blood pressure variability in the enalaprilat group and no change in baroreflex gain, heart rate variability, or blood pressure variability in the control group. CONCLUSIONS: Parasympathetic tone and baroreflex gain increased with parenteral administration of an ACE inhibitor but subsequently decreased below baseline values despite continued suppression of serum ACE activity. The dissociation between ACE suppression and autonomic response to ACE inhibition indicates that enzyme systems not reflected by plasma ACE activity or independent from the classic pathways of angiotensin formation contribute to the regulation of the autonomic response to ACE inhibition in patients with heart failure. The absence of significant change in hemodynamic variables or in blood pressure variability indicates that these autonomic changes are not an indirect reflex response to ACE inhibitor-induced vasodilation or hemodynamic baroreceptor stimulation.     

ACE polymorphisms

Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3' UTR. The potential existence of another functional polymorphism in the 5' UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.     

原发性高血压患者血管紧张素转换酶水平及其基因型关系

目的：观察原发性高血压（ Ｅ Ｈ）患者的血管紧张素转换酶（ Ａ Ｃ Ｅ）水平及其基因型的关系。方法：测定了４５例 Ｅ Ｈ 患者、４３例冠心病（ Ｃ Ｈ Ｄ）患者和４３例健康志愿者血浆 Ａ Ｃ Ｅ水平、 Ａ Ｃ Ｅ 基因型及血浆血管紧张素Ⅱ（ Ａ ＴⅡ）水平。结果：① Ｅ Ｈ、 Ｃ Ｈ Ｄ 和健康对照的各组具有 Ａ Ｃ Ｅ 基因 Ｄ Ｄ型者，血浆 Ａ Ｃ Ｅ水平都高于同组的 Ｉ Ｉ基因型（ Ｐ ＜ ０．００１）和 Ｉ Ｄ 基因型（ Ｐ ＜ ０．０１）；② Ｅ Ｈ Ⅱ期患者中 Ｄ Ｄ 基因型者血浆 Ａ Ｃ Ｅ 水平也高于 Ｉ Ｉ基因型者（ Ｐ ＜ ０．０５），但 Ｅ Ｈ Ⅲ期患者中 Ｄ Ｄ 基因型者，血浆 Ａ Ｃ Ｅ水平和 Ｉ Ｉ、 Ｉ Ｄ 基因型者都无明显差别（ Ｐ ＞ ０．２）；③血浆 Ａ ＴⅡ浓度与 Ａ Ｃ Ｅ 基因型无明显关系。结论：无论 Ｅ Ｈ、 Ｃ Ｈ Ｄ 或健康人，凡具有 Ａ Ｃ Ｅ 基因 Ｄ Ｄ 型的个体，其血浆 Ａ Ｃ Ｅ 水平均有升高，而 Ｉ Ｉ基因型则较低。     

Iron supplementation inhibits cough associated with ACE inhibitors

Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. Generation of NO, a proinflammatory substance on bronchial epithelial cells, is increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may reduce the cough associated with ACEI use. The subjects were 19 patients who had developed ACEI-induced cough. After a 2-week observation period, they were randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The subjects were requested to fill out a cough diary by scoring the daily severity of the cough on a scale of 0 to 4. Mean daily cough scores for the last week of the observation and treatment period were compared. Changes in blood cell count and serum iron and ferritin concentration between the 2 periods were evaluated. Mean daily cough scores during the observation and treatment periods were 3.07+/-0.70 and 1.69+/-1.10, respectively, for the iron group and 2.57+/-0.80 and 2.35+/-1.22, respectively, for the placebo group, showing a significant reduction in cough scores with iron supplementation (P<0.01) but not with placebo. Three subjects in the iron group showed almost complete cough abolition. No significant changes in laboratory data were observed in either group. In conclusion, iron supplementation successfully decreases ACEI-induced cough. This effect may be related to the decrease of NO generation associated with the inhibition of NO synthase activity in bronchial epithelial cells.