小儿肾病综合征血管紧张素I转换酶基因多态性研究

目的探讨ACE基因第16内含子插入/缺失多态性与肾病综合征、血清ACE活性的关系. 方法采用聚合酶链式反应(PCR)检测82例肾病综合征患儿和38例正常儿童ACE基因并同时用酶偶联法测血清ACE活性. 结果①82例肾病综合征患儿中ACE基因II型,ID型和DD型频率分别为47.6%(39/82),24.4%(20/82)和28%(23/82).对照组分别为47.3%(18/38),23.7%(9/38)和29%(11/38),肾病综合征患儿和正常儿童之间ACE基因I/D多态性频率差异无显著性意义(p>0.05).②38例正常儿童和82例肾病综合征患儿血清ACE活性比较差异无显著性意义(p>0.05),ACE各基因型中血清ACE活性差异有显著性意义(p<0.01),DD型>ID型>II型. 结论①小儿肾病综合征ACE基因II型,ID型和DD型频率分布和正常儿童差异无显著性意义(p>0.05).②ACE基因多态性与血清ACE活性密切相关.     

血管紧张素转换酶基因缺失纯合型与糖尿病肾病相关联

应用ＰＣＲ扩增方法检测２０３例ＮＩＤＤＭ患者和１６５例正常对照者血管紧张素（ＡＣＥ）基因的１６内含子中２８７ｂｐ片段缺失／插入多态性。结果显示,糖尿病肾病患者组ＡＣＥ基因缺失纯合型（ＤＤ）频率明显高于非肾病组和正常对照组,Ｐ〈０．００１;ＤＤ缺失纯合型患者肾病进展速度明显快于缺失／插入（ＤＩ）杂合型及插入／插入（ＩＩ）纯合型糖尿病患者,Ｐ〈０．０１。表明ＡＣＥ基因缺失纯合型是糖尿病肾病的独立危险因     

血管紧张素I转换酶基因插入/缺失多态性与人体速度耐力的关联研究

探讨人体血管紧张素I转换酶基因插入/缺失多态性与速度耐力之间的关联性。聚合酶链反应扩增技术检测受试者基因型;测定受试者800 m跑成绩和血乳酸浓度,并对成绩进行逐步聚类分析,将受试者分为高速度耐力组和低速度耐力组。结果发现:高速度耐力组和低速度耐力组组间血管紧张素I转换酶基因型分布及等位基因分布皆无显著性差异(P>0.05);血乳酸浓度无论是安静状态、800 m跑后,还是800 m跑后与安静状态的差值,各基因型组间皆无显著性差异(P>0.05)。人体血管紧张素I转换酶基因插入/缺失多态性与速度耐力无关。     

高血压患者血管紧张素转换酶基因多态性分析

目的探讨血管紧张素转换酶基因多态性与北京房山地区高血压遗传易感相关性。方法应用聚合酶链反应（PCR）技术,检测287例高血压患者和316例正常血压对照者的ACE基因多态性。结果群体相关分析结果表明,高血压组（包括原发性高血压和合并空腹血糖升高的高血压患者）ACE基因的D等位基因及其纯合基因型（D／D）频率较正常血压对照组明显升高（x2＝4．14,P＜0．05）。原发性高血压患者组ACE基因缺失纯合基因型频率较高血压伴有空腹血糖升高组显著增加,其频率分别为30.8％和19．2％（x2＝4．45,P＜0．05）,而高血压伴空腹血糖升高者与对照者间D／D纯合基因型频率无显著差异。结论ACE基因插入／缺失多态性可能与房山地区汉族原发性高血压相关联。     

血管紧张素转换酶基因与心血管疾病

血管紧张素Ｉ转换酶（ＡＣＥ）是肾素－血管紧张素系统（ＲＡＳ）的一个关键酶,为含锌的金属水解酶,ＡＣＥ基因多态性与血循环ＡＣＥ水平密切相关,ＡＣＥ基因可能是ＲＡＳ中与心血管疾病相关的最主要基因之一。ＡＣＥ基因Ｉ／Ｄ多态可能是高血压、冠心病、心肌病、等多种心血管疾病发病的独立危险因素。     

我国人群血管紧张素转换酶基因多态性分布及研究中几个问题

本介绍了ACE基因的生物学特性,ACE基因多态性及我国人群ACE基因分布特点,并对ACE基因与疾病发病机制关系的研究提出了尚需解决的问题。     

我国人群血管紧张素转换酶基因多态性分布及研究中几个问题

本文介绍了 ACE基因的生物学特性、ACE基因多态性及我国人群 ACE基因分布特点 ,并对 ACE基因与疾病发病机制关系的研究提出了尚需解决的问题。     

血管紧张素I转换酶基因多态性与糖尿病视网膜病和糖尿病心肌梗塞关联

目的探讨血管紧张素Ⅰ转换酶(angiotensin Ⅰ-converting enzyme, ACE)基因多态性与糖尿病视网膜病和心肌梗塞之间的关联性.方法应用PCR技术,对1型糖尿病33例视网膜病患者和36例非视网膜病患者、2型糖尿病68例伴心肌梗塞患者和57例伴视网膜病患者以及190例无并发症患者的ACE基因插入/缺失型多态性进行了检测.结果 ACE基因与视网膜病之间无关联.而2型糖尿病心肌梗塞患者与非心肌梗塞患者比较, DD纯合子频率显著增高(41.2% vs 33.2%),D等位基因频率也显著增高,差异有显著性(P<0.05).结论 D等位基因(相对风险为1.50)和DD基因型(相对风险为1.33)可能是2型糖尿病心肌梗塞发生的风险因子.     

广东汉族人群血管紧张素转换酶基因（ACE）多态性研究

目的：探讨中国广东汉族群体血管紧张素转换酶基因（ＡＣＥ）第１６内含子中２８７ｂｐ片段的插入／缺失多态性分布。方法：应用ＰＣＲ扩增技术检测２４４名广东籍汉族人ＡＣＥ基因型。结果：广东汉族群体中ＡＣＥ基因插入纯合型Ｉ／Ｉ占４１％;插入和缺失杂合型Ｉ／Ｄ占４０％,缺失纯合型Ｄ／Ｄ占１９％;Ｉ与Ｄ等位基因出现频率分别为０．６２和０．３９。经Ｘ２检验男女之间无显著性差异（Ｐ＞０．０５）。本组资料Ｉ／Ｉ、Ｉ／Ｄ、Ｄ／Ｄ型三种基因频率与中国汉族人群ＡＣＥ基因多态性分布比较均无显著性差异（Ｐ＞０．０５）与日本人群比较发现日本人与广东汉族人Ｉ／Ｉ、Ｉ／Ｄ、Ｄ／Ｄ三种基因分布频率均无显著性差异（Ｐ＞０．０５）。与欧洲英、法、德三国人群比较发现国人的Ｄ／Ｄ发生频率低于上述三国。Ｉ／Ｉ型发生频率则明显高于欧洲三国。结论：本组资料对ＡＣＥ基因Ｉ／Ｄ多态性分析可能有助于从基因水平对防治ＡＣＥ酶相关疾病进行前瞻性研究具有多方面的应用价值。     

血管紧张素转换酶基因多态性与壮族人高血压和冠心病关联研究

目的：探讨血管紧张素转换酶（ACE）基因多态性与壮族人原发性高血压、冠心病的易感相关性。方法：应用聚合酶链反应技术测定40例正常汉族人、40例正常壮族人、40例壮族冠心病患者、42例壮族高血压患者的ACE基因I／D多态性领率。结果：①正常壮族人与正常汉族人ACE基因I／D频率差异无显著性（＞0．05）。②壮族人冠心病组、高血压组与正常汉族人、正常壮族人的ACE基因型分布差异有显著性,其D／D型分别为0．475、0．43、0．15、0．175。结论：ACE基因缺失型多态性（DD）可能与壮族人冠心病、高血压的发生有关,可能是其遗传易感性基因标志。     

冠心病与ACE基因多态性的相关性研究

为研究血管紧张素转移酶（angiotensin coverting enzyme,ACE)基因插入/缺失（insertion/deletion,I/D)多态性与冠心病（coronary artery disease,CAD)的相关性，我们对105例CAD患者{其中50例合并原发性高血压（essential hypertension,EH）}和102例正常人以多聚酶链反应（polymerase chain reaction,PCR)方法检测其ACE基因多态性。发现CAD组（含合并EH）与正常对照组比较，ACE基因型无显著差异，CAD组（不含合并EH）与CAD组（合并EH）比较，ACE基因型无显著差异，CAD组（不含合并EH）或CAD组（合并EH）分别与正常对照组比较，ACE基因型也无显著差异。提示ACE基因I/D多态性与CAD及CAD合并EH均无相关性。     

妊娠高血压综合征患者血管紧张素转化酶基因多态性研究

目的探讨血管紧张素Ⅰ转化酶（ＡＣＥ）基因第１６内含子插入／丢失多态性与妊娠高血压综合征（简称妊高征）的关系。方法应用聚合酶链反应,检测６０例妊高征患者及对照组７６例正常孕妇的ＡＣＥ基因中第１６内含子是否有Ａｌｕ重复结构存在。结果６０例妊高征患者中ＡＣＥ基因Ｉ型和ＤＤ型频率分别为１５％（９／６０）和６５％（３９／６０）,而７６例正常晚期妊娠妇女中则分别为５０％（３８／７６）和１０．５％（８／７６）。妊高征组的缺失型（Ｄ型）ＡＣＥ等位基因出现频率为０．７５,高于对照组的０．３０８,差异有显著性（Ｐ＜０．０１）。结论提示Ｉ型基因是妊高征的保护性基因,ＤＤ型基因是妊高征的易感基因,ＡＣＥ基因的缺失多态性（ＤＤ）可能与妊高征的发病有关。     

H型高血压患者血管紧张素转化酶基因多态性对其活性及血脂水平影响的探究

目的 探究H型高血压患者和普通高血压患者中不同基因型的血管紧张素转化酶的活性差异以及其对血脂水平的影响.方法 实验采用了聚合酶链式反应的方法,分别鉴定68例H型高血压患者和64例普通型高血压患者血管紧张素转化酶的基因型,并且对不同基因型的血管紧张素转化酶的活性和对应的血脂水平进行了检测.结果 利用SPSS19.0对数据进行分析,H型高血压和普通高血压患者的不同基因型的血管紧张素转化酶活性的差异均具有统计学意义(P＜0.01),但血管紧张素水平的差异无统计学意义.血管紧张素转化酶基因多态性对血脂水平影响的研究表明,H型高血压组中缺失型纯合子(DD型)与插入型杂合子(ID型)和插入型纯合子(Ⅱ型)相比较,DD型血脂水平明显偏高,其中胆固醇(TC)(P＜0.01),高密度脂蛋白(HDLD),低密度脂蛋白(LDLC)和载脂B的水平的差异均具有统计学意义(P＜0.05).普通高血压组仅HDLC,LDLC和载脂B的差异具有统计学意义(P＜0.05).结论 在H型高血压和普通型高血压患者中,血管紧张素转化酶的基因多态性与血管紧张素转化酶的活性及血脂含量有关.H型高血压患者的DD型的血管紧张素转化酶的活性最高,并且血脂水平偏高,其中胆固醇含量增高最为明显,更加容易患高血脂症.     

血管紧张素转换酶基因多态性和酗酒与缺血性脑卒中的关联

目的探讨血管紧张素转换酶（ACE）基因多态性和酗酒与缺血性脑卒中（IS）发病风险的关系。方法应用聚合酶链反应（PCR）和变性高效液相色谱（DHPLC）技术筛查了454例IS患者（病例组）和334例非IS患者（对照组）的ACE基因的多态分布，采用非条件Logistic回归模型分析基因型、酗酒情况与缺血性脑卒中患病的关系。结果与对照组相比，酗酒群体的DD基因型和D等位基因的频率显著性升高（P〈0．05），患缺血性脑卒中的相对危险度分别为8．130和2．488；而携带有Ⅱ基因型的酗酒群体患缺血性脑卒中的相对危险度则为0．389。相反。非酗酒IS患者的ACE基因的各基因型和等位基因频率的分布与对照组相比，均无显著性差异（P〉0．10）。结论携带有D等位基因的酗酒群体容易患缺血性脑卒中，但携带有I等位基因的酗酒群体不容易患缺血性脑卒中。ACE基因与酗酒在缺血性脑卒中的发病过程中存在协同作用。     

Impact of Angiotensin Converting Enzyme Inhibitor versus Angiotensin Receptor Blocker on Incidence of New-Onset Diabetes Mellitus in Asians

Purpose

Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) are associated with a decreased incidence of new-onset diabetes mellitus (NODM). The aim of this study was to compare the protective effect of ACEI versus ARBs on NODM in an Asian population.

Materials and Methods

We investigated a total of 2817 patients who did not have diabetes mellitus from January 2004 to September 2009. To adjust for potential confounders, a propensity score matched (PSM) analysis was performed using a logistic regression model. The primary end-point was the cumulative incidence of NODM, which was defined as having a fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5%. Multivariable cox-regression analysis was performed to determine the impact of ACEI versus ARB on the incidence of NODM.

Results

Mean follow-up duration was 1839±1019 days in all groups before baseline adjustment and 1864±1034 days in the PSM group. After PSM (C-statistics=0.731), a total 1024 patients (ACEI group, n=512 and ARB group, n=512) were enrolled for analysis and baseline characteristics were well balanced. After PSM, the cumulative incidence of NODM at 3 years was lower in the ACEI group than the ARB group (2.1% vs. 5.0%, p=0.012). In multivariate analysis, ACEI vs. ARB was an independent predictor of the lower incidence for NODM (odd ratio 0.37, confidence interval 0.17-0.79, p=0.010).

Conclusion

In the present study, compared with ARB, chronic ACEI administration appeared to be associated with a lower incidence of NODM in a series of Asian cardiovascular patients.     

Polymorphisms in the Angiotensin Converting Enzyme Gene and Growth in the First Year of Life

Abnormal patterns of fetal and infant growth have been associated with an increased risk of cardiovascular disease in adulthood. Catch‐up growth during the first year of life has been associated with a higher prevalence of type 2 diabetes mellitus, whereas a lack of catch‐up growth tracks with a risk of hypertension. The role of genetic factors influencing both growth and blood pressure have not been explored. We genotyped cord blood samples from 530 singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of 1650 pregnancies, and related polymorphism in the angiotensin converting enzyme (ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth and at age of 1 year. ACE genotype did not significantly influence size at birth, although there was a greater proportion of individuals with the D/D genotype born with a birth weight less than the 10^th centile (P = 0.004). The ACE I/I genotype was significantly associated with higher weight (p = 0.001), body mass index (p = 0.001) and mid arm circumference (p = 0.001) at 1 year of age compared to the ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch‐up (gain from birth size of ≥0.6 Standard Deviation Score) in weight (p = 0.04), body mass index (p = 0.03) and mid arm circumference (p = 0.03) compared to the D/D group, the majority of which showed no change or catch‐down. The I/D genotype was distributed equally across the catch up/catch down/no change categories. The effect was more marked in males, but ACE genotype and sex of the infant contributed independently to mid arm circumference measurements and there was no interaction between the two. There was no effect of maternal or paternal ACE genotype on birth size. In a multiple linear regression model ACE genotype, socioeconomic status and sex of the infant explained 10.9% of the variance in body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is associated with a higher weight and body mass index SDS at 1 year of age, along with catch‐up in terms of these measures from birth to 1 year. The D/D genotype is associated with a greater proportion of babies, born at term, that at small for gestational age. These results suggest that due consideration should be given to the underlying genotype of an individual when evaluating the association of early human growth with the development of risk factors for cardiovascular disease. The observation of independent effects of genotype, sex of the individual and socioeconomic status on postnatal growth suggests the need to develop methodologies for the integration of genetic and environmental factors in causality modelling.     

ACE基因I/D多态性在心血管疾病中的研究进展

血管紧张素转化酶（ACE）是肾素-血管紧张素-醛固酮系统（RAAS）的关键酶，在心血管疾病发生发展中起重要作用。近年来有多个研究探讨ACE基因插入/缺失（insertion/ deletion,I/D）多态性与心血管疾病之间的关系，然研究结果尚存争议。本文主要就ACE基因I/D的多态性及其与心血管疾病关系的研究进展做一综述。