Effect of angiotensin converting enzyme gene polymorphism on the renoprotective responsiveness to benazepril in diabetic nephropathy

Objective To test the potential role of an insertion/deletion polymorphism of angiotensin converting enzyme (ACE) gene on the renoprotective responsiveness to benazepril in type 2 diabetes mellitus with nephropathy.Methods The insertion/deletion polymorphisms of ACE gene were determined by polymerase chain reaction(PCR).Ninety cases with diabetes nephropathy were classified according to the genotype of the ACE gene into 30 cases with II genotypes, 29 with ID and 31 with DD.Mean arterial blood pressure (MABP), urinary albumin excretion rate (UAER), serum creatinine (Scr) and ACE levels were measured before and after the six-month treatment of benazepril (no differences in drug dose between groups).Results At baseline the three groups with different genotypes were similar with regard to sex, age, duration of diabetes, frequency of retinopathy, body mass index, HbA(1)c, MABP, UAER, serum creatinine, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, insulin dose.The dose of benazepril and the number of patients receiving nifedipine after starting ACEI were also similar in the patients with II, ID, DD genotypes, respectively.The serum levels of ACE in patients with DD genotype were the highest, the intermediate with ID and the lowest with II genotype (P<0.05).Initiation of 6-month treatment with benazepril induced a significant drop in MABP,UAER and ACE levels in all three groups (P<0.05),but the reduction was significantly greater in patients with II genotype (UAER57.9%, MABP21.4 mm Hg, ACE 74.8%), compared to patients with either ID or DD genotype (P<0.01, respectivly).A mild increase in the serum creatinine was seen in all groups after the initiation of benazepril, but the rate of increase in DD group was the highest (8 .9%) and in II group lowest (5.4%) (P<0.05).A multiple linear regression analysis revealed that the ACE gene polymorphism influenced the decline in albuminuria after initiation of ACE inhibition (R(2)=0.69, P<0.001).Conclusion The patients with II genotype are particularly susceptible to commonly advocated renoprotective treatment.     

Effect of angiotensin converting enzyme gene polymorphism on the renoprotective responsiveness to benazepril in diabetic nephropathy

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ACE基因多态性与高血压患者脑梗塞的关系

目的 搪塞血管紧张素转换酶（ＡＣＥ）基因插入／缺失（Ｉ／Ｄ）与高血压患者并发脑梗塞的关系。方法 应用多聚酶锭式反应（ＰＣＲ）方法对原发性高血压ＥＨ）患者１８２例（其中并发脑梗塞６１例）和对照组５０例正常人的ＡＣＥ基因Ｉ／Ｄ多态性进行检测。结果 高血压患者并发脑梗塞组的ＤＤ基因型及Ｄ等位基因频率（０．５２和０．６５）明显高于高血压无伴发脑梗塞组（０．３２和０．４７）和对照组（０．３０和０．４６）,高     

我国汉族正常人群血管紧张素转换酶基因多态性的观察

目的：探讨我国汉族人群血管紧张素转换酶（ＡＣＥ）基因多态性的分布特点。方法：应用聚合酶链反应研究了１５９名我国汉族正常人群ＡＣＥ基因多态性分布情况。ＡＣＥ基因１６内含子内２８７ｂｐ片段的存在或缺失作为多态性的标志。结果：我国汉族正常人ＡＣＥ的ＤＤ、ＩＤ、ＩＩ基因型频率分别为０．１５７、０．５３５和０．３０８;与国外其他种族人群比较,我国汉族正常人ＤＤ基因型频率显著低于日本人、白种人和黑种人（Ｐ均＜０．０５）。结论：本研究提示,我国汉族正常人ＡＣＥ基因Ｉ／Ｄ多态性分布不同于国外其他种族,我国汉族人ＤＤ基因型频率低于日本人、白种人和黑种人。     

血管紧张素转换酶基因多态性对苯那普利治疗糖尿病肾病疗效的影响

按照血管紧张素转换酶 (ACE)基因插入 /缺失多态性不同 ,将 92例 2型糖尿病肾病患者分为II型组 31例 ,ID型组 30例及DD型组 31例。用苯那普利治疗 6个月后 ,观察治疗前后各组的尿白蛋白排泄率 (UAER)、平均动脉压 (MABP)、肌酐清除率 (Ccr)及ACE的变化。结果 :苯那普利治疗后 3组UAER、MABP、ACE均下降 ,以II型组下降幅度最大 (分别为 58.6%、2 .87kPa和 72 .3% ) ,DD型组下降幅度最小 (P <0 .0 5) ;而Ccr在DD型组下降幅度最大 ,II型组下降幅度最小 (P <0 .0 5) ;多元线性逐步回归分析显示 :ACE基因型对UAER下降率有显著回归效果(R2 =0 .72 ,P <0 .0 0 1 )。提示 :ACE基因型影响血管紧张素转换酶抑制剂 (ACEI)对糖尿病肾病的疗效 ,II基因型患者对ACEI治疗更为敏感。     

血管紧张素转换酶基因多态性与小儿紫癜性肾炎的关系

目的　探讨血管紧张素转换酶多态性 (ACE)与紫癜性肾炎 (HSPN)之间的关系。方法　用PCR方法对HSPN患儿及正常儿童进行ACE基因多态性检测 ,并对不同基因型的HSPN患儿治疗前后的蛋白尿和血尿水平进行比较。结果　HSPN组与正常对照组ACE基因多态性分布比较差异无显著性 (P >0 0 5 ) ;HSPN患儿中DD型表现有大量蛋白尿和明显血尿的频率显著高于II型 ,II型治疗 2个月后蛋白尿和血尿减轻或转阴的频率显著高于DD与DI型。结论　ACE基因多态性可能对HSPN的发生无明显意义 ,但可能与其临床表现中明显的个体差异及治疗后疾病不同的转归有关。     

广东汉族原发性高血压患者ACE基因多态性与ACE、PAI-1活性的相关性

目的 研究广东汉族原发性高血压患者血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与ACE、纤溶酶原激活剂抑制物-1(PAI-1)活性的相关性.方法 应用PCR方法扩增115例广东汉族人群原发性高血压患者及96例健康体检者ACE基因特异性片段,同时应用比色法测定血清ACE活性,发色底物法测定PAI-1活性,并对结果进行相关性分析.结果 (1)高血压组ACE DD基因型频率(34.7%)和D等位基因频率(60.0%)显著高于对照组(15.6%和42.1%)(P均＜0.05).(2)高血压组血清ACE(217.18±57.35 U/L)及血浆PAI-1活性(0.87±0.16 U/ml)均显著高于对照组(169.13±47.64 U/L,0.62±0.18 U/ml)(P均＜0.01);高血压组与对照组ACE与PAI-1活性均呈显著正相关(r分别为0.7913、0.7806,P均＜0.01).(3)高血压组DD基因型血清ACE(257.46±54.73 U/L)、血浆PAI-1活性(0.97±0.16 U/ml)显著高于ID基因型(213.28±51.36 U/L,0.83±0.17 U/ml)及Ⅱ基因型(177.63±51.45 U/L,0.72±0.15 U/ml)(P均＜0.01);D基因型血清ACE、血浆PAI-1活性亦显著高于Ⅱ型(P均＜0.05).结论 (1)DD基因型以及D对位基因可能与广东汉族人群原发性高血压有关;(2)高血压患者血清ACE和血浆PAI-1活性增加,由ACE基因型所决定的ACE活性,可能参与血浆PAI-1水平的调节;(3)高血压患者纤溶受损可能存在一定的遗传背景,ACE基因DD型可能是高血压纤溶紊乱的危险因素.     

Association of polymorphisms in angiotensin-converting enzyme and type 1 angiotensin II receptor genes with coronary heart disease and the severity of coronary artery stenosis

Summary To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels (⩾75% stenosis) and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism (an A→C transversion at nucleotide position 1166) were detected by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in CHD patients and 90 healthy serving as controls. The results showed that DD genotype and of ACE were more frequent in CHD patients than that in control group (38.5% vs 14.4%, P<0.001). The frequency of the AT1R A/C genotypes did not differ between the patients and the controls (10% vs 13.1%, P>0.05). The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes (P>0.05). But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype (P<0.05). In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.     

血管紧张素转换酶基因多态性对血浆血管紧张素Ⅱ水平及心衰的影响

目的：探讨血管紧张素转换酶（ACE）D/I基因多态性对中国人血浆血管紧张素Ⅱ（AngⅡ ）水平的影响,以及是否可影响心衰的发生。方法：用多聚酶链式反应对181例受检者（102例健康体检者、79例慢性心衰患者）进行ACE基因分型,用放射免疫法测定其AngⅡ水平。结果：在181例受检者中,ACE基因多态性与AngⅡ水平有关,AngⅡ水平依次为DD型＞ID型＞II型（P<0.05）。多元逐步回归模型分析表明,校正多种混淆因素后AngⅡ水平仍受ACE基因型影响。ACE基因型在心衰患者和健康对照者中的分布无明显差异。结论：国人ACE D/I基因多态性与AngⅡ水平存在相关,携带DD型ACE基因者AngⅡ水平较高;ACE基因 D/I多态性与慢性心衰的发生无关。     

老年非杓型高血压与 ACE I／D 基因多态性的研究

目的：研究老年非杓型高血压患者与ACE I/D基因多态性的相关性。方法选取96例老年高血压患者应用聚合酶链反应（ PCR）方法检测其ACE I/D基因多态性,然后对其全部进行24小时动态血压监测（ ABPM）,根据ABPM结果分为杓型和非杓型高血压组。结果 DD型在非杓型组比例显著升高,II型在杓型组比例显著升高,有统计学意义, ID型在非杓型组比例高于杓型组,但无统计学意义。结论老年非杓型高血压与ACE基因DD型相关。     

血管紧张素Ⅰ转换酶基因多态性与Ⅱ型糖尿病肾病

用PCR技术对274例无肾病并发症的Ⅱ型糖尿病(NIDDM)、102例Ⅱ型糖尿病肾病合并肾功能不全(RI)、124例Ⅱ型糖尿病肾病无肾功能不全(NRI)、242例正常对照组进行了血管紧张素Ⅰ转换酶(ACE)基因插入/缺失多态性的检测,同时观察血清血管紧张素转换酶(ACE)水平与ACE基因多态性及疾病的关系。结果：RI组D等位基因频率0.52,DD基因型频率0.30,与对照组(0.38,0.16)比较有显着差异(P<0.05,P<0.001);DD基因型较II对RI的比数比为2.91(95%CI为1.52～5.58,P<0.01).NIDDM组及NRI组基因型频率分布与对照组比较无显着差异(P>0.05);各组中DD基因型个体血清ACE水平最高II基因型最低,RI组及NRI组血清ACE水平显着高于对照组(P<0.001),基因多态性与血清ACE水平呈相关性(r=0.65,P<0.01).表明血清ACE水平升高对糖尿病肾病的发生及进展有重要作用,ACE基因缺失多态性可能是中     

血管紧张素1转化酶基因多态性与Ⅱ型糖尿病合并心肌梗死的关系

为探讨血管紧张素 1转化酶 (ACE)基因插入 /缺失多态性与Ⅱ型糖尿病合并心肌梗死 (MI)及无并发症的Ⅱ型糖尿病 (DM2 )的相关情况 ,同时观察血清ACE水平与ACE基因多态性及疾病的关系。对 82例MI、86例DM2和 84例健康人 (对照组 )用PCR方法进行了ACE基因内含子 1 6插入 /缺失多态性的检测 ,用紫外分光光度法测定了血清ACE水平。结果MI组D等位基因频率 0 .52 ,DD基因型频率 0 .32 ,与对照组 ( 0 .36,0 .1 5)比较有显著差异 (P <0 .0 5) ,DD基因型对MI的比数比为 3.0 1 ( 95%可信区间为 1 .2 8～ 7.0 4 ,P <0 .0 1 ) ;DM2组基因型频率分布与对照组比较无显著差异 (P >0 .0 5) ;各组中DD基因型个体血清ACE水平最高 ,II基因型最低 ,基因多态性与血清ACE水平呈相关性 (r=0 .65,P <0 .0 1 )。说明ACE基因缺失多态性参与中国人DM2合并MI的发病 ,是其发病的危险因素     

血管紧张素转化酶基因型及其血清活性与原发性高血压的关系

目的探讨血管紧张素转化酶(ACE)基因型及其血清活性与原发性高血压(EH)的关系.方法以人类基因组DNA为模板,应用聚合酶链式反应(PCR)技术检测120例EH组和93例正常对照组ACE基因第16内含子的插入/缺失(I/D)多态性,并按性别分组计算各组基因型和等住基因频率,另外用比色法测量各研究对象的ACE血清活性.结果男性EH组DD基因型和D等位基因频率均显著高于对照组(均P＜0.05).女性EH组DD基因型频率和D等位基因频率与对照组比较差异无统计学意义(P＞0.05);在EH组中ACE活性与对照组比较差异无统计学意义(P＞0.05);ACE血清活性在ACE基因DD,ID和Ⅱ型间有显著性差异(P＜0.05).结论EH与ACE基因I/D多态性有显著相关性,特别是男性,ACE基因DD基因型可能在EH的发生发展过程中是重要的危险因素之一.ACE血清活性与ACE基因I/D多态性有关.     

Studies on ACE gene insertion/deletion polymorphism, serum ACE activity, and diabetic retinopathy in type II diabetic patients]

To clarify the relationship among angiotensin 1-converting enzyme(ACE) gene insertion/deletion(I/D) polymorphism, serum ACE activity, and diabetic retinopathy in Type II diabetic patients, we examined 36 healthy controls, 40 Type II diabetic patients without diabetic retinopathy, and 68 Type II diabetic patients with diabetic retinopathy. All of patients suffered from Type II diabetes beyond 5 years and matched in age and body mass index. An insertion/deletion polymorphism of ACE gene was identified by polymerase chain reaction(PCR). Serum ACE activity was determined using spectrophotometry. The distribution of DD, ID, and II genotypes of the ACE gene did not differ among the three groups (16.7%, 33.3%, and 50.0% in the healthy controls; 22.5%, 35.0%, and 42.5% in Type II diabetic patients patients without diabetic retinopathy; and 20.6%, 30.9%, and 48.5% in Type II diabetic patients with diabetic retinopathy; respectively). The frequency of ACE I/D genotypes was not significantly different between non-proliferative retinopathy and proliferative retinopathy of Type II diabetic patients with diabetic retinopathy (P > 0.05). Serum ACE activity of three groups was similar (P > 0.05). These results do not support the hypothesis that the DD genotype of the ACE gene would be a clinically useful genetic marker for predicting the development of diabetic retinopathy in Type II diabetic patients. There is no association between ACE gene I/D polymorphism and the prognosis of diabetic retinopathy in Type II diabetic patients. ACE may not involve in forming diabetic retinopathy in Type II diabetic patients.     

新疆维吾尔族ACE基因I/D多态性分析及其血清ACE水平的相关性

目的　调查新疆维吾尔族血管紧张素转换酶 (ACE)基因I/D多态性分布及其血清ACE水平的相关性。方法　通过两次聚合酶链反应测定 81例健康维吾尔族ACE基因。结果　所有被调查的 81例健康维吾尔族人ACE基因中 ,DD型占2 5 9%,DI型占 48 1%,II型占 2 5 9%,D与I等位基因出现频率均为 0 5 0。 3种基因型中 ,DD型个体ACE水平最高 ,DI型者次之 ,II型者最低 ,有统计学意义。结论　维吾尔族ACE基因DD型为 2 5 9%。ACE基因DD型与血清ACE水平显著相关 (P <0 0 5 ) ,维吾尔族ACE基因的DD型同其他民族一样可能通过影响ACE水平而导致心血管疾病发病。     

Possible Association of ACE Gene I/D Polymorphism With Blood Pressure——Lowering Response to Hydrochlorothiazide

Objective To explore the association between polymorphism in the ACE I/D gene and blood pressure-lowering response to hydrochlorothiazide (HCTZ) in 829 patients. Methods HCTZ 12.5 mg was taken once a day for six weeks. The blood pressure reduction and ratio reaching target blood pressure were compared in different ACE genotype groups. Results The reduction in SBP of patients carrying DD was greater than that in other groups carrying II or ID (12.2 mmHg versus 5.4 mmHg, 12.2 mmHg versus 4.4 mmHg, respectively, P<0.05). The reduction in MAP of patients carrying DD was also greater than that in other groups carrying II or ID (6.9 mmHg versus 3.9 mmHg, 6.9 mmHg versus 3.6 mmHg, respectively, P<0.05). The ratio reaching target blood pressure in DD groups was significantly higher than that in II or ID groups (P<0.05). The pre-treatment SBP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of SBP. The pre-treatment DBP, aldosterone levels, DD genotype entered the multi-linear regression model significantly and might affect the reduction of DBP. The pre-treatment MAP, DD genotype, aldosterone levels entered the multi-linear regression model significantly and might affect the reduction of MAP. Conclusion ACE genotyping is associated with blood pressure-lowering response to HCTZ. Specific genotypes might be associated with the response to specific antihypertensive treatment.     

肥厚型心肌病患者血管紧张素转换酶基因缺失多态性研究

目的 探讨血管紧张素转换酶（ＡＣＥ）基因插入／缺失（Ｉ／Ｄ＿多态必瑟肥厚型心肌病（ＨＣＭ）发病的关系。方法 应用ＰＣＲ技术扩增ＡＣＥ基因目的片段检测基因多态性。结果 ＨＣＭ患者与正常对照组的Ｄ等位基因频率及ＤＤ基因型分布有显著性差异（Ｐ〈０．０１,Ｐ〈０．０５）,ＤＤ基因型ＨＣＭ患者心脏事件发生率及左室壁厚度明显大于２、ＩＤ基因型ＨＣＭ患者（Ｐ〈０．０５,Ｐ〈０．０１）,家族性肥厚型心肌病（ＦＨＣ     

上海地区老年人ACE基因多态性频率的分布

目的 研究血管紧张素转换酶（ACE）基因插入（Ⅰ）／缺失（D）多态性在上海地区正常老年人群中的分布。方法 利用PCR三条引物法对478例上海地区正常人进行ACE I／D基因型的分析比较,其中老年人（＞60岁）344例。结果 上海地区正常人的ACE I／D基因型分布是：Ⅱ型47．70％,ID型43．51％,DD型8．79％。在老年人群中的分布频率分别为47．09％、43．61％、9．30％,各基因型频率与新加坡人、日本人、台湾地区、香港的华人接近,但与白种人和非洲裔人群差异显著。结论 ACE基因多态性的分布与年龄无关,但有明显的种族和地区差异。     

血管紧张素转换酶基因多态性与糖尿病肾病ACEI疗效的影响

目的探讨血管紧张素Ⅰ转换酶（ＡＣＥ）基因多态性与糖尿病肾病ＡＣＥ抑制剂（ＡＣＥＩ）疗效的相关性。方法随机挑选了３１例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、５８例ＮＩＤＤＭ合并肾病患者和５０例正常人,用ＰＣＲ方法检测ＡＣＥ基因的缺失／插入的多态性。结果ＮＩＤＤＭ组、ＮＩＤＤＭ合并肾病组和正常人群三组之间,ＡＣＥ基因的几种基因型分布差异无显著意义。对４０例ＮＩＤＤＭ合并肾病患者用ＡＣＥ抑制剂治疗,有效１９例,其中ＤＤ型８例,ＤＩ型２例,Ⅱ型９例;无效２１例,其中ＤＤ型１例,ＤＩ型３例,Ⅱ型１７例（Ｐ＜００１）。结论ＮＩＤＤＭ合并肾病ＡＣＥＩ疗效,ＤＤ型最好,Ⅱ型最差。ＡＣＥＩ基因Ｄ／Ｉ多态性有助于糖尿病肾病ＡＣＥＩ疗效的判定     

血管紧张素Ⅰ转换酶基因多态性与慢性心力衰竭药物治疗效果

目的：探讨血管紧张素Ⅰ转换酶（ACE）基因多态性对慢性心衰治疗效果的影响。方法：79例慢性心衰患者,用多聚酶链式反应（PCR）进行ACE基因分型,得到II,ID,DD三种基因型。所有患者用放射免疫法测定AngⅡ水平,超声测定左室舒张末期内径（LVDD）、左室射血分数;经常规方法治疗后,复查上述指标,并比较不同ACE基因型的治疗效果。结果：DD型慢性心衰患者LVDD,AngⅡ水平较其余两型患者更大、更高,且治疗后AngⅡ水平的下降幅度最大（P<0.05）。结论：国人ACE I/D基因多态性与慢性心衰的治疗效果可能有关。DD型患者体内可能存在较高的内分泌激活水平,经相关的药物治疗后可能获得更有益的内分泌效应。