血管紧张素转换酶和血管紧张素原基因多态性与冠心病的关系

目的探讨血管紧张素转换酶（ACE）插入／缺失（I／D）多态性和血管紧张素原（AGT）M235T基因多态性与冠心病（CHD）的关系。方法应用多聚酶链反应结合限制性内切酶法（PCR—RFLP）对110例冠心病患者、62例冠状动脉造影正常者以及18名门诊常规体检无冠心病史者基因多态性进行分析。结果①CHD组ACE基因DD基因型及D等位基因频率明显高于健康对照组（分别为43．6％、60．5％比26．3％、44．4％）,差异有统计学意义‘P〈0．05）。CHD组AGT基因TT基因型及T等位基因频率明显高于对照组（分别为66．4％、78．6％比42．5％、60．6％）,差异有统计学意义（尸〈0．05）。②男性CHD组ACE基因DD基因型和D等位基因频率以及AGT基因TT基因型和T等位基因频率均显著高于对照组（均P〈O．05）。女性CHD组ACE基因DD基因型和D等位基因频率以及AGT基因‘rr基因型和T等位基因频率与对照组比较差异无统计学意义（P〉0．05）。③联合分析ACEDD型及AGTTr型罹患冠心病的相对风险,其比数~L（OR）为4．904,高于单基因ACEDD型（2．175）及AGTTT型（2．669）。结论ACE基因I／D多态性及AGT基因M235T多态性与CHD有显著相关性,同时具有ACEDD型及AGT TT型发生冠心病的相对风险显著高于单基因ACEDD型及单基因AGT‘丌型。性别也可作为冠心病的危险因素。     

肾素-血管紧张素系统双基因多态性与老年人冠心病慢性心力衰竭的关系

目的:探讨中国南方部分汉族人群的老年冠心病患者中,肾素-血管紧张素系统中的关键成分即血管紧张素转换酶(ACE)及血管紧张素原(AGT)双基因多态性与慢性心力衰竭(心衰)发病的关系.方法:应用聚合酶链反应及限制性片断长度多态性技术,对396例老年冠心病患者的ACE基因插入/缺失(I/D)及AGT基因M235T多态性进行检测.将其中196例合并慢性心衰患者作为病例组,其余200例心功能正常者作为对照组.结果:①病例组DD基因型频率及D等位基因频率均高于对照组;②病例组TT基因型频率及T等位基因频率均高于对照组;③联合分析ACE与AGT基因多态性显示,两组中同时具有DD型ACE基因及TT型AGT基因的频率分别为28.6%及15.0%,前者明显高于后者.结论:DD型ACE基因及TT型AGT基因可能是中国南方部分汉族老年冠心病慢性心衰患者发病的遗传危险因素,ACE和AGT基因在慢性心衰的发生中具有协同作用.     

肾素-血管紧张素系统双基因多态性与高血压合并舒张性心力衰竭的关系

目的探讨中国南方部分汉族高血压患者肾素一血管紧张素系统中血管紧张素转换酶（ACE）及血管紧张素原（AGT）双基因多态性与舒张性心力衰竭发病的关系。方法应用聚合酶链反应及限制性片断长度多态性技术,对432例高血压患者的ACE基因插入／缺失（I／D）及AGTM235T多态性进行检测。将其中207例合并舒张性心力衰竭者作为病例组,其余225例心功能正常者作为对照组。结果①病例组DD基因型及D等位基因的频率均高于对照组;②病例组TT基因型及T等位基因的频率与对照组比较差异无统计学意义;③联合分析ACE与ACT基因多态性显示,两组中同时具有DD型ACE基因及TT型AGT基因的频率分别为29．0％及14．9％,前者明显高于后者。结论DD型ACE基因可能是该地区高血压患者舒张性心力衰竭发病的遗传危险因素,ACE和AGT基因在慢性心力衰竭的发生中具有协同作用。     

肾素-血管紧张素系统基因多态性与冠心病合并慢性心力衰竭严重程度的关系

目的检测部分中国南方汉族人群冠心病合并慢性心力衰竭患者的ACE及AGT基因多态性分布情况,以探讨肾素-血管紧张素系统（1／AS）基因多态性对冠心病合并慢性心力衰竭严重程度的影响。方法应用聚合酶链反应及限制性片断长度多态性技术,对210例冠心病合并慢性心力衰竭患者的ACE基因插入／缺失（I/D）及AGT基因M235T多态性进行检测,采用彩色多普勒检测患者的左室舒张末内径（LVDD）及左室射血分数（LVEF）。结果不同ACE基因型患者其LVDD及LVEF均存在差异,LVDD（DD）〉LVDD（ID）〉LVDD（II）（P〈0．05）,LVEF（DD）〈IXEF（ID）〈LVEF（II）（P〈0．05）,不同AGT基因型亚组间LVDD及LVEF差别均无统计学意义（P〉0．05）。结论ACE基因I／D多态性与中国南方部分汉族人群冠心病合并慢性心力衰竭的严重程度相关,DD型ACE基因的冠心病患者发生心力衰竭后病情较其他基因型者更加严重。AGT基因M235T多态性似与冠心病合并慢性心力衰竭的严重程度无关。     

肾素-血管紧张素系统基因多态性与冠心病的关系

目的探讨肾素-血管紧张素系统三个关键基因血管紧张素转化酶基因插入/缺失多态性、血管紧张素原基因M235T多态性及血管紧张素Ⅱ1型受体基因A1166/C多态性与冠心病的关系。方法应用多聚酶链反应-限制片长多态性方法对110例冠心病患者和80例健康人分别进行单基因和基因连锁分析。结果①冠心病组血管紧张素转化酶基因DD基因型(43.6%)及D等位基因频率(60.5%)明显高于正常对照组(分别为26.3%和44.4%,P<0.05);血管紧张素原基因TT基因型(66.4%)及T等位基因频率(78.6%)亦明显高于正常对照组(分别为42.5%和60.6%,P<0.05);与正常对照组相比,冠心病组血管紧张素Ⅱ1型受体基因的AA、AC基因型频率和A、C等位基因频率差异均无显著性(P>0.05)。②联合分析三个基因多态性罹患冠心病的相对风险,其OR为3.395,高于单基因血管紧张素转化酶DD型(OR为2.175)及血管紧张素原TT型(OR为2.669),低于血管紧张素转化酶DD型 血管紧张素原TT型(OR为6.098)。结论血管紧张素转化酶基因插入/缺失多态性及血管紧张素原基因M235T多态性与冠心病有关,而血管紧张素Ⅱ 1型受体基因A1166/C多态性可能与冠心病无关联。同时具有血管紧张素转化酶DD型及血管紧张素原TT型者发生冠心病的相对风险显著增高。     

中国苗族人群血管紧张素原和血管紧张素转化酶基因多态性与冠心病的关系

目的 研究血管紧张素原(ACT)基因M235T分子变异和血管紧张素转化酶(ACE)基因I/D多态性与冠状动脉粥样硬化的关系.方法 采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)技术检测冠心病(CHD)组151例和正常对照组127例AGT基因多态性,采用聚合酶链反应技术检测CHD组151例和正常对照组127例ACE基因I/D多态性.结果 CHD组AGT-TT基因型频率为76.26%,显著高于对照组44.10%(P<0.01).ACE-DD基因型频率为35.10%,显著高于对照组14.96%(P<0.01).结论 在中国苗族人群中,AGT基因TT基因型和AGE基因DD基因型是CHD发病既相互独立又具有协同作用的危险因子.     

血管紧张素原基因和血管紧张素转换酶基因多态性与高血压

目的　研究中国人群中血管紧张素原 (AGT)基因单核苷酸多态性 (SNP)及血管紧张素转换酶 (ACE)基因插入 /缺失多态与高血压病的关系。方法　在 3 4 5例高血压病患者与 2 0 6名血压正常人中采用PCR RFLP法检测AGT基因A 2 0C ,A 6G和M 2 3 5T的多态性 ,用PCR法检测ACE基因 16内含子Alu片段插入 /缺失多态 ,同时用EM算法进行两位点连锁不平衡分析。结果　在M 2 3 5T和A 2 0C ,M 2 3 5T和A 6G ,A 2 0C和A 6G位点观察到了连锁不平衡 (P <10 - 4)。病例 对照检验显示T2 3 5等位基因频率在高血压组中高于对照组 ,且高血压病患者中ACE (DD +ID) +AGT TT2 3 5基因型频率高于对照组。结论　受检人群中AGT基因各多态频率处于两两连锁不平衡 ,但AGT基因即T2 3 5位点以隐性作用方式与高血压关联 ,T2 3 5等位基因与ACE D等位基因在高血压病发生中具协同作用     

桂西地区壮族人群肾素—血管紧张素系统基因多态性分析

目的探讨肾素—血管紧张素系统（RAS）中血管紧张素Ⅱ1型受体（AT1R）基因A1166C多态、血管紧张素Ⅰ转化酶（ACE）基因插入/缺失（I/D）多态及血管紧张素原（AGT）基因M235T多态在桂西地区壮族人群中的分布频率,比较其在不同种族间分布的差异。方法采用PCR-RFLP技术和DNA测序法检测150例壮族人AT1R基因A1166C、ACE基因I/D和AGT基因M235T多态性,结合文献进行不同种族间的比较分析。结果桂西地区壮族人群AT1R基因A1166C基因型和等位基因频率与土耳其比较差异有统计学意义;桂西地区壮族人群ACE基因I/D基因型频率与法国人、土耳其人比较差异有统计学意义,基因型和等位基因频率与黎巴嫩人、巴林人比较差异有统计学意义;桂西地区壮族人群AGT基因M235T基因型和等位基因频率与法国人、蒙古族人、土耳其人、波兰人比较有统计学差异（P均〈0.01）。结论 RAS基因多态性在不同种族间分布频率存在差异,这种差异势必会影响RAS基因在一些疾病特别是地方高发性疾病发生、发展中的作用。     

不同性别高血压病患者肾素-血管紧张素系统多基因多态性关联研究

目的探讨不同性别高血压病患者与肾素-血管紧张素系统,包括血管紧张素Ⅱ-1型受体(AT1R)基因、血管紧张素转化酶(ACE)和血管紧张素原(AGT)多基因多态性的相关性。方法应用多聚酶链式反应-限制性酶切法(PCR-RFLP)检测95例高血压病患者和98例健康对照者的AT1R基因1166位点、ACE基因I/D以及AGT基因M235T基因型,比较不同性别两组间基因型和等位基因型的分布频率。结果男性高血压组AT1R基因、AC/CC基因型和ACE基因DD基因型频率高于对照组,1166C和D等位基因频率明显高于对照组;AGT基因TT基因型及T等位基因频率较对照组为高,但差异无统计学意义;在女性,ACE基因D等位基因频率较其对照组为高(P0.05),余各基因型和等位基因频率在病例组与对照组之间均未见差异。结论肾素-血管紧张素系统多个基因位点变异与男性高血压病发病有关,只有较少基因位点多态性参与女性发病。     

冠心病患者血管紧张素转换酶基因多态性及其与血清血管紧张素转换酶水平的关系

为研究冠心病患者血管紧张素转换酶（ACE）基因插入／缺失（I／D）多态性分布及其与血清ACE水平的相关性，应用多聚酶链反应方法测定了61例冠心病患者和63例健康人群的ACE基因I／D多态性，并采用微量比色法测定其血清ACE水平。结果发现，冠心病患者ACE基因DD型出现频率显著高于对照组，且DD基因型者具有较高的血清ACE水平。提示ACE基因I／D多态性与血清ACE水平密切相关，DD型ACE基因可能是中国人冠心病发病的独立危险因子。     

血管紧张素原基因T174M和血管紧张素转换酶基因I/D多态性与急性心肌梗死的相关性

目的探讨中国汉族人群血管紧张素转换酶和血管紧张素原基因型的分布及其与急性心肌梗死的关系。方法应用聚合酶链反应技术,对112例急性心肌梗死患者、128例非冠心病患者血管紧张素转换酶I/D多态性及血管紧张素原T174M多态性进行检测。结果血管紧张素转换酶基因型分布及等位基因频率在病例组及对照组间差异有显著性(P<0.01)。病例组和对照组血管紧张素原基因型及等位基因频率总体分布差异亦有显著性(P<0.05)。联合基因分析显示,急性心肌梗死组血管紧张素转换酶DD基因型 血管紧张素原174MM基因型频率显著高于对照组(P<0.01),具有该联合基因型者发生冠心病的风险比数比(OR=8.467)明显高于单独具有血管紧张素转换酶DD基因型(OR=2.558)或血管紧张素原174MM基因型(OR=6.176)者。结论血管紧张素原T174M基因多态性中M等位基因和血管紧张素转换酶I/D基因多态性基因中的D等位基因是中国汉族人群冠心病发病的危险因素之一。同时具有血管紧张素转换酶DD型及血管紧张素原174MM型发生冠心病的相对风险显著高于单基因血管紧张素转换酶DD型及单基因血管紧张素原174MM型。     

Interaction between gene polymorphisms of renin-angiotensin system and metabolic risk factors in premature myocardial infarction

The renin-angiotensin system is involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The authors investigated the association of genetic variability in the renin-angiotensin system (RAS) with premature MI and interactive effects between gene polymorphisms and metabolic risk factors on MI risk. Their study compared 142 patients with MI younger than 55 years with 142 healthy subjects. Polymorphisms of angiotensin-I converting enzyme (ACE) gene (insertion/deletion), angiotensinogen gene (M235T), and angiotensin-II type-1 receptor (AGT1R) gene (A1166C) were tested. The ACE-DD (deletion/deletion) genotype conferred a twofold independent risk for MI (confidence interval [CI] = 1.1-3.7; p = 0.01) after adjustment for cardiovascular risk factors, whereas angiotensinogen-TT genotype and AGT1R-AA genotype were not independent risk factors for MI. An interactive effect on MI risk was found between ACE-DD and AGT1R-AA genotypes (odds ratio [OR]=2, 95% CI= 1-3.9), between ACE-DD and angiotensinogen-TT genotypes (OR = 2.7, 95% CI = 1-7.3), as well as among ACE-DD, angiotensinogen-TT, and AGT1R-AA genotypes (OR=4.8, 95% CI = 1-22.8). Similarly, metabolic risk factors interacted with angiotensinogen-TT genotype (OR= 2, 95% CI = 1.1-3.9) on MI risk. The ACE-DD genotype is an independent risk factor for MI in patients younger than 55 years. Additionally, the authors provide evidence of an interactive effect on MI risk between risk genotypes of RAS, as well as between the angiotensinogen-TT genotype and metabolic risk factors.     

Angiotensinogen gene T235 variant: a marker for the development of persistent microalbuminuria in children and adolescents with type 1 diabetes mellitus

AIM: We examined genetic polymorphisms in the renin-angiotensin system (RAS) coding for angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) for angiotensinogen (AGT) M235T and angiotensin II receptor type 1 (AGTR1) A1166C as predictors for the development of microalbuminuria (MA) in children with type 1 diabetes mellitus (T1DM). METHODS: Four hundred fifty-three (215 males, 238 females) T1DM children [median (interquartile range): age, 16.7 years (13.9-18.3); diabetes duration, 6.9 years (3.3-10.8); age at diagnosis, 9.1 years (5.8-11.8)] were followed prospectively from diagnosis until the development of MA (two of three consecutive overnight urine samples with albumin excretion rates of > or =20 and <200 microg/min). Kaplan-Meier survival curves and Cox proportional multivariate model estimated the probability of developing MA and the relative risk for MA among different variables. RESULTS: MA developed in 41 (9.1%) subjects. The frequencies of genotypes were as follows: ACE-II 112 (25%), ACE-ID 221 (49%), and ACE-DD 117 (26%) (n=450); AGT-MM 144 (32%), AGT-MT 231 (51%), and AGT-TT 77 (17%) (n=452); AGTR1-AA 211 (47%), AGTR1-AC 204 (45%), and AGTR1-CC 37 (8%) (n=452). The cumulative risk for the development of MA was higher in ACE-DD versus ACE-ID/II groups (log-rank test, P=.05), and a trend was noticed when AGT-TT was compared to AGT-MT/MM groups (log-rank test, P=.08). AGT-TT polymorphism conferred a fourfold increased risk for MA compared to AGT-MM/MT (hazard ratio=3.8; 95% confidence interval=1.43-10.3; P=.008). INTERPRETATION: Our findings suggest that RAS gene polymorphism at AGT M235T is a strong predictor for early MA in young T1DM subjects.     

基因芯片技术分析老年冠心病患者的易感基因

目的 研究血管紧张素转换酶（ACE）、血管紧张素原（AGT）及内皮型一氧化氮合酶（eNOS）基因多态性与老年人冠心病（CHD）的关系.方法 选择老年CHD患者100例及对照者91例,应用基因芯片技术检测ACE、AGT和eNOS基因多态性,并比较其基因型及等位基因频率。结果 CHD组ACE DD基因型频率（28.0%）与对照组（15.4%）比较，差异有统计学意义（P＜0.05）,ACE基因多态性与老年CHD相关.AGT TT基因型频率（75.0%）与对照组（51.7%）比较，差异有统计学意义（P＜0.01）,AGT基因多态性与老年CHD相关.eNOS TT基因型频率（5.0%）与对照组（0.0%）比较,差异无统计学意义（P＞0.05）。同时携带ACE DD和AGT TT基因型或AGT TT和eNOS TT基因型者与老年CHD呈显著正相关（OR=2.9,P＜0.05,OR=1.1,P＜0.05）。结论 ACE和AGT基因多态性可能是中国老年人CHD的危险因素。     

Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients

Purpose

Whether the renin–angiotensin–aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly.

Methods

The study included one hundred and seventeen acromegalic patients (62 F/55 M, age: 50.2?±?12.3 years) and 106 healthy controls (92 F/14 M, age: 41.4?±?11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype.

Results

The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16–60) vs. 12 (5–36) µg/L, p?<?0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p?<?0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow A_peak values than T allele carriers (0.94?±?0.46 vs. 0.73?±?0.20; p?=?0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms.

Conclusions

Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.

     

Sex difference in the effect of ACE-DD genotype on the risk of premature myocardial infarction

In this association study the authors compared the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism in females and males with premature myocardial infarction (MI). I/D ACE gene polymorphism was tested in 738 subjects: 302 patients with MI (151 men and 151 women) and 436 healthy subjects (207 men and 229 women). In women the ACE-DD genotype was not associated with MI (OR 1.1, 95% CI 0.6-2.1, p=0.6), whereas the ACE-DD genotype conferred a 2-fold independent risk for MI in men (95% CI=1.2-3.4; p=0.013) after adjustment for cardiovascular risk factors. The authors found evidence for the sex difference in the effect of the ACE-DD genotype on MI risk. The ACE-DD genotype conferred a 2-fold independent risk for premature MI in males.     

Distribution of different HLA antigens in Greek hypertensives according to the angiotensin-converting enzyme genotype

The angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is an independent risk factor for cardiovascular disease. It has also been suggested that some HLA genes may contribute to the genetic susceptibility to essential hypertension. So far, an association between ACE polymorphism and HLA antigens in arterial hypertension has not been reported. We have studied 94 subjects with newly diagnosed essential hypertension, 49 men and 45 women (mean age, 52.3 ± 11.3 years), as well as 104 randomly selected, age- and gender-matched normotensive individuals (54 men and 50 women, mean age 48.7 ± 10.8 years). Both cohorts originated from the Greek population and lived in the greater Athens area. The ACE genotype was analyzed by polymerase chain reaction. HLA class I and II antigens were studied by serologic and molecular techniques.The prevalence of the ACE genotypes did not differ significantly between hypertensives and normal individuals. The casual blood pressure levels and the average ambulatory blood pressure levels were similar among the three ACE genotypes. Hypertensives with the ACE-DD genotype were characterized by an increased prevalence of the HLA-A2 antigen (50% v 31.4%, P < .005) and DR6 (16.7% v 11.4%, P < .01) in comparison to the normotensive subjects with the ACE-DD genotype. HLA-A24 was found more frequently among the hypertensives with the ACE-ID genotype than in the normal controls with the same genotype (35.5% v 26.4%, P < .05). ACE-DD genotype is associated with a high prevalence of specific HLA antigens. The coexistence of the ACE-DD genotype with certain HLA phenotypes could reveal a distinct hypertensive population with increased risk for cardiovascular events.