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。     

血管紧张素原、血管紧张素转换酶和内皮型一氧化氮合酶基因多态性与脑梗死的相关性研究

目的探讨中国人群血管紧张素原(AGT)、血管紧张素转换酶(ACE)和内皮型一氧化氮合酶(eNOS)基因多态性与脑梗死的相关性。方法应用基因芯片技术联合检测114例脑梗死患者和76例正常对照者AGT基因M235T、ACE基因I/D和eNOS基因G894T多态性位点,分别对两组的基因型及等位基因频率进行统计学分析。结果①脑梗死组AGT基因TT型、ACE基因DD型、eNOS基因TT型频率均比对照组显著升高,结果分别为65.79%vs47.37%,P=0.012;25.44%vs13.16%,P=0.040;7.89%vs1.32%,P=0.047;②AGTT等位基因、ACED等位基因、eNOST等位基因频率也明显高于对照组,结果分别为82.02%vs71.71%,P=0.018;52.19%vs34.21%,P=0.001;18.86%vs9.21%,P=0.010。③AGT、ACE和eNOS基因多态性联合分析显示脑梗死组AGTTT ACEDD、AGTTT eNOSTT、ACEDD eNOSTT基因型频率与对照组无显著性差异,结果分别为11.40%vs5.26%,P=0.146;6.14%vs1.32%,P=0.105;1.75%vs1.36%,P=0.100。结论AGT、ACE和eNOS基因多态性可能是中国南方汉族人群脑梗死的遗传危险因素,但AGT、ACE和eNOS基因在脑梗死的发生中不具有交互作用,并不增加脑梗死发生的危险机率。     

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.     

ACE及AGT基因多态性与糖尿病肾病发病风险的关系

目的探讨血管紧张素转换酶(ACE)基因和血管紧张素原(AGT)基因多态性与糖尿病肾病(DN)发病风险之间的关联。方法根据筛选标准选择DN患者100例编入DN(+)组,选择2型糖尿病(T2DM)无合并DN患者100例编入DN(-)组,同时选择健康者200例编入对照组。采用PCR技术选择性扩增及电泳检测ACE及AGT M235T基因。结果 ACE基因检测中,DN(+)与DN(-)在基因型及等位基因分布频率上无统计学差异(P0.05),而DM组与对照组基因型及等位基因分布频率具有明显差异(P0.01);AGT M235T基因检测中,DN(+)与DN(-)在AGT基因型及等位基因分布频率上无显著差异(P0.05),DM组与对照组基因型及等位基因分布频率无显著差异(P0.05);联合多态性分析结果显示,DD+TT基因型对于DN(+)OR值为4.042(95%CI 1.717~9.515),DD+TT对于DN(-)OR值为3.171(95%CI 1.306~7.698)。结论 DN受多基因遗传因素影响,单个基因变异对DN发病影响程度有限。而ACE-DD基因型与AGT-TT基因型可能存在协同作用,促使DN发病风险上升。     

连锁分析血管紧张素转换酶基因插入/缺失多态性和血管紧张素原 M235T基因多态性与肥厚型心肌病的关系

目的 连锁分析中国人群血管紧张素转换酶（ACE）基因插入／缺失多态性及血管紧张素原（AGT）M235T基因多态性与肥厚型心肌病（HCM）发病的关系。方法 对63例HCM患分别用PCR法检测ACE基因插入／缺失和AGT M235T基因多态性。结果 HCM患中ACE DD＋AGT TT基因型的比数比高于单基因型,其心脏事件发生率高于其他基因型组合和AGT TT型。结论 同时具有ACE DD＋AGT TT基因型,较单基因型发生HCM的风险率显增高;同时具有ACE DD＋AGT TT基因型的HCM患发生心脏事件的危险更大。     

基因芯片技术分析与冠心病的相关基因

目的评估血管紧张素原(angiotensinogen,AGT)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)和载脂蛋白E(apolipoprotein E,ApoE)多态性与冠心病的关系,并分析AGT、eNOS和ApoE基因多态性在冠心病的发生和发展中是否存在协同作用。方法选择冠心病患者133例及对照者154名,用基因芯片技术检测AGT、eNOS和ApoE基因多态性,并对比其基因型及等位基因频率。结果冠心病组AGT TT和eNOS TT基因型频率与对照组相比差异有统计学意义,分别为OR=2．63,P<0．001,OR=8．50,P< 0．05。AGT和eNOS基因多态性与冠心病相关。同时携带AGT TT和eNOS TT基因型者与冠心病密切相关(OR=1．05,P<0．01)。ApoE基因型频率及等位基因频率与对照组相比差异无统计学意义(P>0．05)。结论AGT和eNOS基因多态性可能是中国人冠心病的危险因素,基因芯片技术为研究多种易感基因与冠心病的相关性提供了一项高效、敏感的方法。     

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.     

原发性高血压相关基因多态性的临床分析

目的 研究中国南方汉族人群中血管紧张素原(AGT235)、血管紧张素转换酶(ACEI/D)、心钠素(ANP2238)、C型心钠素受体(NPRC-55)和内皮型一氧化氮合酶(eNOS298)基因多态性与原发性高血压(EH)的关系.方法 选择EH患者81例及对照者120例,采用基因芯片技术检测AGT235、ACEI/D、ANP2238、NPRC-55、eNOS298基因多态性,并比较其基因型及等位基因频率. 结果 EH组AGT235 TT基因型频率(53.1%)与对照组(45.8%)无差异(P>0.05);EH组患者ACEI/D DD基因型频率(48.1%)与对照组(4.2%)差异显著(P<0.001);EH组ANP2238CC基因型频率为6.1%,与对照组(8.3%)无差异(P>0.05);EH组NPRC-55CC基因型频率为65.4%,对照组(68.3%)无差异(P>0.05);EH组eNOS298DD基因型频率为3.7%,与对照组(0.8%)无差异(P>0.05).结论 ACEI/D基因可能是EH的易感基因,AGT235、ANP2238、NPRC-55和eNOS298基因与EH不具有相关性.     

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。     

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。     

Renin-angiotensin system gene polymorphisms: assessment of the risk of coronary heart disease

BACKGROUND: Renin-angiotensin system genes are candidate genes in cardiovascular system diseases. Angiotensinconverting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) gene polymorphisms are considered risk factors in coronary heart disease (CHD). AIM: To evaluate the involvement of the ACE, AGT and AT1R genetic variants in predisposition to CHD as well as their association with other known risk factors. METHODS: The study included 400 male subjects (200 with CHD and 200 healthy individuals). Genotypes were determined by a polymerase chain reaction (PCR). For the AGT and AT1R genes a restriction analysis of the PCR product was performed. The allele frequency and genotype distribution were compared between groups. RESULTS: The allele and genotype frequencies of the ACE gene were similar in both groups, however, a significantly higher frequency of the DD genotype was observed in the presence of hyperlipidemia (39% vs 24% in non-hyperlipidemic subjects, p<0.01). The AGT gene polymorphism was associated with the development of CHD. The T allele was significantly more frequent in patients than in the control group (55% vs 44%, p<0.05). The heterozygous MT genotype was observed in 61% of patients compared to 40% in the controls (p<0.05). The A1166C polymorphism of the AT1R gene was also associated with CHD as well as with age at the onset of disease. The frequency of the C allele was 29% compared to 21% in the control group (p<0.01) and the frequency of the CC homozygote was almost three times higher in patients. CONCLUSIONS: There is an association between molecular variants of the angiotensinogen and angiotensin II type 1 receptor and increased risk of CHD. The DD genotype of the ACE gene polymorphism and the TT genotype of the AGT gene polymorphism were significantly more frequent in patients with hyperlipidemia. The TT genotype of the AGT gene M235T polymorphism was associated with an increased risk of CHD and myocardial infarction only in smokers.     

Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms.

BACKGROUND: Polymorphisms within renin angiotensin system genes have been investigated as risk factors for coronary artery disease in different populations with contradicting results. The aim of this study was to investigate the genotype distribution and the allele frequencies of ACE, AT1R and AGT gene polymorphisms as coronary artery disease factors and their synergistic effects on coronary risk in an Italian population. METHODS AND RESULTDS: In this study ACE, AT1R and AGT gene polymorphisms were investigated in 205 consecutive coronary artery disease patients and in 209 controls. These polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The ACE D and AGT 235T allele, but not AT1R C allele, frequency was statistically significant in patients. An association between coronary artery disease and ACE DD, AT1R CC and AGT TT genotype, was found by univariate analysis (OR 2.06 P=0.0007, OR 2.49 P=0.009, OR 1.87 P=0. 019, respectively). At multivariate analysis ACE DD and AT1R CC genotype (OR 1.81 P=0.011, OR 2.61 P=0.011, respectively) remained associated with coronary heart disease. Subjects carrying the ACE DD genotype and AT1R C allele showed a stronger association with myocardial infarction (OR=4.02, P<0.0001). CONCLUSION: Our report indicates the increased risk of coronary artery disease in the presence of ACE DD and AT1R CC genotypes independent of other risk factors, in Italian patients. The present study stresses the relevance of screening for genetic risk factors.     

Endothelial nitric oxide synthase gene influences the risk of pre-eclampsia, the recurrence of negative pregnancy events, and the maternal-fetal flow

OBJECTIVES: Pre-eclampsia is associated with vascular endothelial dysfunction, adverse pregnancy outcome and cardiovascular disease in later life. An inadequate nitric oxide availability related to polymorphisms in the endothelial nitric oxide synthase gene (eNOS) might predispose to the disease. METHODS: We investigated the role of eNOS T-786C, G894T and 4a4b polymorphisms in predisposing to both pre-eclampsia and the recurrence of negative pregnancy events, per se and in the presence of angiotensin-converting enzyme (ACE) DD genotype, and investigated their influence on maternal-fetal flow in 106 non-thrombophilic women with a history of pre-eclampsia, compared with 106 women with a history of normal pregnancy. RESULTS: No association between eNOS polymorphisms and predisposition to pre-eclampsia was found; nevertheless, the contemporary presence of eNOS 894TT and -786CC genotypes represented a susceptibility factor to the disease. In 48 out of 106 women, documented complications (pre-eclampsia and fetal growth restriction) were present in the current pregnancy. The eNOS 894TT genotype influenced the risk of recurrence of negative events (odds ratio = 5.45), particularly in contemporary women homozygous for both eNOS 894TT and ACE DD genotypes (odds ratio = 11.4). Throughout the pregnancy, a progressive alteration of maternal-fetal flow indices was found in women carrying the eNOS 894TT genotype, and this effect was strengthened in women with the contemporary presence of the ACE DD genotype. CONCLUSIONS: An original finding is the increased risk of pre-eclampsia and recurrence of pregnancy negative events, probably by modulating the maternal-fetal flow, in women homozygous for the eNOS 894T allele previously analyzed for the ACE I/D polymorphism.     

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.     

Angiotensin converting enzyme gene polymorphisms and coronary risk in a Portuguese population]

BACKGROUND: A family history of coronary heart disease (CHD) is a strong risk marker for the disease, independently of classical risk factors. It could be decoded by recognizing the polymorphisms associated with increased risk. Renin-angiotensin system genes are candidate genes in CHD and the deletion allele of the angiotensin converting enzyme (ACE) has been reported as deleterious. However, there is disagreement as to the role of the insertion/deletion polymorphism of the ACE gene in coronary risk. AIM: To evaluate whether ACE gene polymorphisms constitute a CHD risk factor. METHODS: We conducted a population-based case-control study of 301 subjects with a history of myocardial infarction or angiographic evidence of coronary heart disease and 510 age- and gender-matched controls, without CHD, living in a region with high CHD mortality rates. Blood samples were taken, DNA extracted and genotypes determined by the polymerase chain reaction (PCR). Amplification products were identified by agarose gel electrophoresis. STATISTICAL ANALYSIS: The Data were evaluated by SPSS for Windows, using the Student's t test, the chi-square test, odds ratios and 95% confidence intervals. RESULTS: The prevalence of the DD, ID and II genotype was 41.2%, 46.3%, 12.5% in the cases and 28.1%, 55.2% and 16.7% in the control group. The frequency of the DD genotype was significantly higher in the cases than in the controls (41.2% vs. 28.1%, odds ratio 1.79, 95% CI 1.31 to 2.4, p < 0.0001). By contrast, the ID and II genotypes' prevalence was higher in the control group (55.2% vs. 46.3%, p = 0.002 and 16.7 vs. 12.5%, p = NS, respectively) compared to the case group. CONCLUSIONS: This study clearly shows that the ACE DD polymorphism is strongly linked to CHD, and if our data are confirmed in a larger population sample, more aggressive vascular prevention could be justified in patients carrying the DD genotype.     

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.

     

Polymorphism of Angiotensin Converting Enzyme, Angiotensinogen, and Apolipoprotein E Genes in a Japanese Population With Cerebrovascular Disease

The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the ε4 allele of the apolipoprotein E gene (apoE/ε4) are reported to be associated with ischemic heart disease. Cerebrovascular disease (CVD) is another atherosclerotic disease; and the effects of these polymorphisms on CVD have been confusing. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/ε4 genotypes are associated with CVD and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with cerebral infarction (n = 55) and cerebral hemorrhage (n = 38), diagnosed by brain computed tomography. Control subjects for the infarction group and the hemorrhage group were randomly selected from 583 subjects matched for age, gender, and history of hypertension with patients. Frequency of ACE/DD genotype was higher in the patients with infarction than in the controls (χ² = 6.1, P < .05). The AGN/TT genotype was not associated with either infarction or hemorrhage, but it increased the relative risk for cerebral infarction in the subjects with ACE/DD genotype (χ² = 8.0, P < .01, odds ratio; 11.7, 95% confidence intervals: 1.4 to 96.0). There was no significant association between apoE/ε4 and CVD. These results suggest that ACE/DD predicts cerebral infarction, but not cerebral hemorrhage, and that AGN/TT enhances the risk for cerebral infarction associated with ACE/DD.