血管紧张素转化酶基因I/D多态性与脑梗死后抑郁相关

目的 探讨北京地区汉族人群血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与脑梗死后抑郁(PCID)发病的关系.方法 用汉密尔顿抑郁量表评定664例脑梗死患者抑郁状态,用PCR方法检测患者ACE基因I/D多态性,分析基因多态性分布与脑梗死后抑郁发病的相关性.结果 脑梗死后抑郁患者组ACE基因I/I基因型频率和I等位基因频率(分别为0.388和0.549)显著高于脑梗死后非抑郁患者对照组(C)(分别为0.286和0.481,P＜0.05).结论 ACE基因I/D多态性与脑梗死后抑郁发病相关,ACE I/I基因型可能是脑梗死后抑郁发病的危险因素.     

脑卒中患者血管紧张素转换酶基因多态性与心率变异性的关联研究

目的　探讨脑卒中患者血管紧张素转换酶 (angiotensin- converting enzyme,ACE)基因多态性和心脏心率变异性的关系。方法　应用聚合酶链反应方法检测 4 3名正常人、4 6例脑梗塞患者、4 0例脑出血患者 ACE基因的插入 /缺失多态性 (insertion/deletion,I/D) ,并用心率变异性 (heart rate variability,HRV)分析方法观察其 HRV的时域、频域和混沌参数。结果　缺血性、出血性脑卒中患者的 ACE基因缺失型 (DD)及 D等位基因频率明显高于正常对照组 (P<0 .0 1) ,DD型患者的 HRV的参数值升高 ,即相邻心搏间期的均方根值、相邻心搏间期差大于 10 ms的心搏间期数占心搏间期总数的百分比、总功率谱、高功率谱、低频功率谱、混沌参数 ,明显高于 ACE基因插入型 (II)、ACE基因插入 /缺失混合型 (ID)患者 ,差异有显著性 (P<0 .0 5 )。结论　 HRV的相关参数和遗传相关 ,提示脑卒中患者有 ACE DD基因型的人 ,有脑源性心脏自主神经功能紊乱发生的危险性。     

Effects of angiotensin-converting enzyme inhibition and bradykinin peptides in rats with myocardial infarction

Background and objective: Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease myocardial remodeling and faciliate cardiac function improvement in the setting myocardial infarction by affecting bradykinin. The purpose of this study was to evaluate the combination effects of perindopril and bradykinin (BK) in rats with myocardial infarction. Methods: Wistar Rats underwent to left anterior descending (LAD) coronary artery ligation were allocated into MI group (n = 6); Perindopril group (n = 7); Perindopril + BK group (n = 7). An additional sham operation group (Sham group, n = 6) were also established. After 4 weeks, the left ventricle function, myocardial tissue morphology, myocardial collagen volume faction, infracted ventricular wall thickness, myocardial infarction area and neovascular formation were evaluated. Results: Combination treatment with perindopril and BK were showed significant improvement on LVEDV, LVEF and LVFS than MI group. Moreover, a significant improvement on LVEF was found in Perindopril + BK group than Perindopril group but not on LVEDV and LVFS between these two groups. Furthermore, neo-vessel density was significantly increased in Perindopril + BK group than other groups while no significant improvement on vessel density was found after the treatment of perindopril. In addition, myocardial infarction thickness improvement was found in Perindopril and group than MI group while combination treatment with perindopril and BK can significant improve the myocardial infarction thickness than perindopril only. Conclusions: Combination treatment with ACE inhibitor perindopril and BK can significantly improve the ventricle function in the rat model of myocardial infarction. Our data suggest BK can serve as adjuvant treatment in myocardial infarction treatment.     

Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and myocardial infarction

Bøhn M, Berge KE, Bakken A, Erikssen J, Berg K. Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and myocardial infarction.
Clin Genet 1993: 44: 292–297. © Munksgaard, 1993
Male (n = 185) and female (n = 49) survivors of myocardial infarction (MI) below 56 and 61 years of age, respectively, were compared to 366 controls with respect to distribution of genotypes in an insertion/deletion (ID) polymorphism at the angiotensin I-converting enzyme (ACE) locus. The frequency of the DD genotype (homozygosity for the deletion allele) was significantly lower among male patients than controls (22.7% versus 34.9%, p = 0.011). In a "low-risk" group, defined as having less than the sex-specific, age-adjusted median values of body mass index (BMI) and apolipoprotein B (apoB), respectively, and absence of treatment with lipid-lowering drugs, the prevalence of the DD genotype was not statistically different between male patients and controls. In a male "high-risk" group (those individuals who had not been defined as "low-risk" subjects), the prevalence of the DD genotype was 20.9% in patients and 38.3% in controls (p = 0.002). In women, no significant differences in genotype frequencies between patients and controls were found in the whole sample or in any subgroup. These results appear to be at variance with data reported recently by Cambien et al. (1992). The difference may be due to chance, undetected selection biases, different gene-environment interactions between Norway and France or Ireland, or to preferential loss of DD individuals in our male "high-risk" group.     

心肌梗死患者血管紧张素转换酶基因多态性与ACE、PAI-1活性的相关性

目的:研究心肌梗死(MI)患者血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与ACE、PAI-1活性的关系。 方法: 应用PCR方法扩增93例MI患者及87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:①MI组ACE DD基因型频率(32.3%)和D等位基因频率(54.3%)显著高于对照组(12.6%和37.4%)(均P<0.01)。②MI组血清ACE(216.00±58.26)U/L及血浆PAI-1活性(0.85±0.19)AU/mL均显著高于对照组(170.19±48.99)U/L, (0.66±0.20)AU/mL(均P<0.01)；MI组与对照组ACE与PAI-1活性均呈显著正相关(r分别为0.7108，0.7829,均P<0.01)；③MI组DD基因型血清ACE(251.64±57.76)U/L、血浆PAI-1活性(0.96±0.16)AU/mL显著高于ID基因型(211.47±51.87)U/L，(0.82±0.18)AU/mL及Ⅱ基因型(179.84±52.65)U/L，(0.71±0.17)AU/mL(均P<0.01)；ID基因型血清ACE、血浆PAI-1活性亦显著高于Ⅱ型(P<0.05)。对照组DD基因型血清ACE(195.53±54.76)U/L、血浆PAI-1活性(0.78±0.20)AU/mL，显著高于II基因型(154.98±52.74)U/L，(0.59±0.17)AU/mL(均P<0.05)。 结论:由ACE基因所决定的ACE活性，可能参与血浆PAI-1水平的调节；ACE基因I/D多态性与ACE、PAI-1水平相关，ACE基因种类影响纤溶平衡，这可能是其促使MI发病的重要机制之一。     

Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma

BACKGROUND: Nitric oxide, including that produced by endothelial constitutive nitric oxide synthase (ecNOS), may regulate vascular and airway tone in the lungs and may influence various aspects of airway homeostasis. Angiotensin-converting enzyme (ACE) is expressed at high levels in the lungs and plays a role in the metabolism of angiotensin II, bradykinin, and substance P, all of which are potentially involved in the pathogenesis of asthma. An insertion-deletion polymorphism of the ACE gene has been shown to be associated with enzyme activity levels of ACE. To examine the possible involvement of the ecNOS and/or ACE genes as the genetic basis of bronchial asthma, we investigated whether there was any association between bronchial asthma and polymorphisms of the ecNOS and/or ACE genes. METHODS: A total of 310 patients with bronchial asthma and 121 healthy subjects took part in this study. The ecNOS and ACE genotypes were determined in all subjects by polymerase chain reaction. RESULTS: 1) The distribution of one genotype (bb) of ecNOS was significantly higher in the asthma group than in the control population. 2) The ACE genotype distribution was not significantly different between the control and the asthma groups. 3) In asthmatic patients, the ACE and ecNOS genotype distribution did not differ significantly among groups of patients with different severities of asthma. CONCLUSIONS: These results suggest that polymorphisms of the ecNOS gene, but not the ACE gene, may be associated with the development of asthma. However, the severity of asthma may not be influenced by polymorphisms of the ecNOS and ACE genes.     

microRNA-208在急性心肌梗死患者外周血中的表达及意义

目的:通过分析microRNA-208在急性心肌梗死(acute myocardial infarction,AMI)患者外周血中含量的变化,探讨microRNA-208在AMI疾病进展中的作用.方法:连续性收集2013年1月~2013年12月滁州市第一人民医院心血管内科和急诊科收治的急性心肌梗死(AMI)患者42例,不稳定心绞痛(unstable angina,UA)患者22例,健康体检志愿者20名,荧光定量 PCR测定外周血microRNA-208的含量,电化学发光法检测血浆cTnI和CK-MB的水平.AMI组患者根据不同冠脉病变支数和接受急诊经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗进行分组,对比各组患者外周血microRNA-208水平的差异.结果:AMI患者外周血microRNA-208的水平显著高于UA组和健康对照组,差异具有统计学意义(P<0.01),AMI患者外周血microRNA-208的水平与血清CTnI含量呈正相关(r=0.700,P=0.000).24例行冠状动脉造影术的AMI组患者中,microRNA-208的表达在两支及三支病变中高于单支病变(P<0.01),17例成功接受急诊PCI治疗的AMI患者,其症状发作后的24h血浆microRNA-208水平较入院即刻时明显降低(P<0.01).结论:心肌细胞特异性的microRNA-208在心肌梗死后外周血含量明显升高,随着血管狭窄严重程度的升高其浓度也显著变化,可以作为辅助监测急性心肌梗死的敏感的生物学指标.     

Insertion /deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and parental history of myocardial infarction

Bøhn M, Berge KE, Bakken A, Erikssen J, Berg K. Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and parental history of myocardial infarction.
Clin Genet 1993: 44: 298–301. © Munksgaard, 1993
One hundred and eighty-one male and 48 female myocardial infarction (MI) survivors and 172 male and 194 female controls were studied with respect to a possible association between premature parental MI (before age 61 years in mothers and/or before age 56 years in fathers) and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). In the total series, the frequency of premature parental MI was 14% in the DD (homozygotes for the deletion (D) allele) genotypic group, 10.6% in the ID (heterozygotes) genotypic group and 6.1% in the II (homozygotes for the insertion (I) allele) genotypic group. In all males (male MI survivors and male controls combined), and in the total series, there was a significant excess of DD individuals as compared to II individuals among those with a parental history of premature MI (odds ratio 3.1 (p = 0.03) and 3.1 (p = 0.009), respectively). The ACE polymorphism may be an important genetic marker of MI risk and contribute to clustering of premature MI in families.     

Monoclonal antibodies to native mouse angiotensin-converting enzyme (CD143): ACE expression quantification, lung endothelial cell targeting and gene delivery

We demonstrated previously that the monoclonal antibody 9B9 to angiotensin-converting enzyme (ACE), which accumulates very selectively into the rat lung after systemic injection, is a powerful tool for immunotargeting of therapeutic agents or genes to the rat lung vascular bed. Bearing in mind a high research and therapeutic potential of lung targeting via ACE, we obtained a new set of rat monoclonal antibodies to different epitopes of mouse ACE in order to expand this approach to mice. Nine new monoclonal antibodies, recognizing epitopes on the N- and C-domains of catalytically active mouse ACE, were obtained and examined for their efficacy to bind ACE both in vitro and in vivo. This set of monoclonal antibodies was proved to be useful for ACE quantification (by flow cytometry and cell enzyme-linked immunosorbent assay) on the surface of different mouse ACE-expressing cells: endothelial cells, monocytes, macrophages, dendritic cells and spermatozoa. Moreover, gene delivery into mouse ACE-expressing cells using adenoviruses increased 40-fold after redirecting of these viruses to ACE (by coating these viruses with anti-ACE monoclonal antibodies). Radiolabelled (I(125)) monoclonal antibodies specifically accumulated in the mouse lung after systemic injection. Monoclonal antibodies 3G8.17, 4B10.5 and 4B10.17 demonstrated the highest level of lung uptake, 40-50% of injected dose, and high selectivity of lung uptake. Influence of monoclonal antibodies on ACE shedding was negligible, except monoclonal antibody 1D10.11. None of the tested monoclonal antibodies inhibited ACE activity in vitro. In conclusion, a new set of rat monoclonal antibodies to mouse ACE was obtained suitable to study ACE biology in mice and for ACE expression quantification on mouse cells in particular. These monoclonal antibodies also demonstrated highly efficient and selective lung accumulation and thus has the potential for targeting drugs/genes to the pulmonary vasculature in different mouse models of human lung diseases, including numerous knockout models.     

ACE、AGT基因联合多态性与高血压合并脑梗塞相关

目的探讨北京地区汉族人群血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与血管紧张素原(AGT)基因CD235Met-Thr变异(M235T)与高血压合并脑梗塞发生的关系。方法分别用PCR法、突变基因分离聚合酶链反应(MS-PCR)法检测664例高血压合并脑梗塞患者(CI),678例单纯高血压患者(EH)和716例对照者(C)的ACE基因I/D多态性及AGT基因M235T多态性,分析两个基因多态性分布与高血压合并脑梗塞发病的相关性。结果 CI组ACE-DD和AGT-TT基因型频率(分别为0.309和0.643)均显著高于C组(分别为0.203和0.543,P<0.001)和EH组(分别为0.217和0.569,P<0.01)。CI组与C组比较,ACE-DD、AGT-TT联合基因型OR值(2.547,95%CI:1.919～3.382)明显高于ACE-DD单基因型(1.759,95%CI:1.376～2.248)和AGT-TT单基因型(1.515,95%CI:1.220～1.880)。结论 ACE-DD和AGT-TT基因型与北京地区汉族人群单纯高血压发病无相关性,但与高血压合并脑梗塞发病显著相关,并且A...     

The influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglyceride levels and risk of myocardial infarction

The importance of an APOAV gene for plasma triglyceride level determination has been shown on transgenic and knockout mice. We examined whether APOAV variants are associated with plasma triglyceride levels and risk of myocardial infarction (MI). We have evaluated the influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglycerides in 1191 males and 1368 females representatively selected from the Czech population. Triglycerides have been analysed in 1997 and 2001. Subsequently, we have analysed the genotype frequencies of the APOAV polymorphism in 435 patients with MI. T-1131>C variation in the APOAV gene affects the plasma triglyceride showing a higher level in C-1131 carriers than in T/T-1131 homozygotes. This association has been observed both in males and females (p < 0.001). Similarly, plasma triglycerides were also significantly influenced by the S19>W APOAV genotypes. In both males and females, the W19 carriers have triglycerides significantly (p < 0.001) higher compared to the S19 homozygotes. In a group of MI patients, the frequency of the rare homozygotes for at least one APOAV polymorphism (C/C-1131 and/or W/W19) was significantly higher than that in the population sample (7.4 vs 2.0%, p < 0.00001). We conclude that variations in the APOAV gene not only play a role in genetic determination of triglyceride levels but also could influence risk of MI.     

Association of a polymorphism of the ecNOS gene with myocardial infarction in a subgroup of Turkish MI patients

In this study we examined a possible association between a 27 base pair (bp)-repeat polymorphism in intron 4 of the ecNOS gene and myocardial infarction (MI) in a subgroup of the Turkish population. We compared MI and control groups for the frequencies of the ecNOS alleles and their genotypes. The frequency of the ecNOS 4a/a and 4a/b genotypes was found to be significantly higher in the MI group than in the control group. Interestingly, the frequency of the ecNOS 4a/b polymorphism was found to be significantly higher in the selected MI group (patients with no known secondary risk factors) than in the control and non-selected MI group. We found that the patients with MI had the frequency of the a/a genotype 4.3%, of the a/b genotype 26.6% and the b/b genotype 69.1%. The controls, however, showed only 0.6% for a/a, 18.0% for a/b and 81.4% for the b/b genotype (P < 0.001; chi2 = 13.626). In this study, we show that myocardial infarction is associated with one subtype of ecNOS gene polymorphism.     

A DNA polymorphism at the angiotensin II type 1 receptor (AT1R) locus and myocardial infarction

Two hundred and thirty-five survivors of myocardial infarction (MI) were compared to 384 controls with respect to distribution of genotypes and gene frequencies in the A1166C polymorphism at the angiotensin II type 1 receptor (AT1R) locus. No differences in allele frequencies or genotype distribution were observed when all patients were compared with all controls. When comparing CC homozygotes with the combined group of CA heterozygotes and AA homozygotes (CA/AA), a difference in borderline significance between the MI group and controls was observed (p = 0.05). In males alone, this difference was much more pronounced because of the larger proportion of males with the CC genotype in MI cases than in male controls (p = 0.01). No significant differences were observed between female cases and controls. No interaction between the insertion/deletion (I/D) polymorphism at the angiotensin I-converting enzyme (ACE) locus and the polymorphism at the AT1R locus was detected. When subdividing the subjects into a "low-risk" and a "high-risk" group, based on levels of apolipoprotein B (apoB) and body mass index (BMI), and whether or not the person used lipid-lowering drugs, the frequency of CC homozygotes in male cases of the "low-risk" group differed significantly compared to the frequency in male controls of the "low-risk" group (p < 0.001). No differences were observed in females, but the number of "low-risk" group female cases was low (n = 3). Thus, CC homozygosity appears to be associated with MI in Norwegian males, especially among those with a "low-risk" phenotype.     

四川南部汉族人群血管紧张素转换酶基因多态性对血管紧张素转换酶抑制剂抗蛋白尿作用的影响

目的　探讨四川南部汉族人群血管紧张素转换酶(angiotensin- coverting enzyme,ACE)基因多态性与血管紧张素转换酶抑制剂治疗原发性慢性肾小球肾炎蛋白尿疗效的相关性。方法　用苯那普利治疗99例伴有蛋白尿的原发性慢性肾小球肾炎患者,疗程为3个月。用PCR方法检测ACE基因第16内含子的插入/缺失(insertion/ deletion,I/ D)多态性,比较血管紧张素转换酶抑制剂治疗前后各基因型患者尿蛋白定量下降程度的差异。结果　治疗前ACE基因DD型组尿蛋白显著高于II型组(P<0 .0 5 ) ;苯那普利治疗3月后,DD、ID型组的尿蛋白定量下降幅度明显高于II型组(P<0 .0 5 )。结论　苯那普利可以改善原发性慢性肾小球肾炎患者的尿蛋白,且降低尿蛋白的疗效与患者的ACE基因型有明显的相关性。     

Association of essential hypertension in elderly Japanese with I/D polymorphism of the angiotensin-converting enzyme (ACE) gene

Recent evidence suggests that an insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) is associated with myocardial infarction and related cardiovascular diseases. We investigated a possible association of the ACE polymorphism with essential hypertension in a total of 263 cases/controls from among the elderly (age, over 70 years) and middle-aged (age between 30 and 60 years) Japanese population. The frequency of the I/I homozygote was significantly higher in hypertensive subjects than in controls in the elderly age group (33/57 vs 16/46; P = 0.02), but no association was observed in the middle-aged group (25/75 vs 26/85; P = 0.71). Similarly, having at least one insertion allele was associated with essential hypertension in the elderly age group (83/114 vs 46/92 in controls; P = 0.001), but not in the middle-aged group (78/150 vs 94/170; P = 0.524). These data suggest that genetic variation at the ACE locus may be associated with some determinants for blood pressure in elderly persons, and imply the involvement of the ACE insertion/deletion polymorphism in the etiology of age-related essential hypertension in the Japanese population. Received: April 18, 2000 / Accepted: July 25, 2000     

血管紧张素原及血管紧张素转化酶基因多态性与高血压之间的关系

目的 研究血管紧张素原基因（ａｎｇｉｏｔｅｎｓｉｎｏｇｅｎ,ＡＧＴ）第２外显子Ｍ２３５Ｔ等位基因的变异及血管紧张素转换酶（ａｎｇｉｏｔｅｎｓｉｎ ｃｏｎｖｅｒｔｉｎｇ ｅｎｚｙｍｅ,ＡＣＥ）基因多态性、在中国正常人群及原发性高血压（ｅｓｓｅｎｔｉａｌ ｈｙｐｅｒｔｅｎｓｉｏｎ,ＥＨ）患者中的频率分布,分析基因在ＥＨ中的发病作用。方法 应用多聚酶链反应结合限制性酶切方法,对９５例健康体检者和８７例Ｅ     

Lack of association of angiotensin I-converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians

Eighty-five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early-onset MI was found in this population group. Other gene components of the renin-angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.     

中国汉族人ACE基因多态性与心肌梗塞及梗塞后室性心律失常的关系探讨

目的：探讨血管紧张素转换酶（ACE）基因多态性与心肌梗塞及梗塞后室性心律失常的关系。方法：应用聚合酶链反应技术测定110例心肌梗塞患者、159名汉族正常人的ACE基因插入/缺失多态性。结果：(1) 心肌梗塞患者ACEDD基因型及D等位基因频率显著高于正常人（均P<0.05），DD与非DD及D与I的比数比分别为12.70(1.094-1.474)及1.194(1.011-1.411)。(2) 心肌梗塞组患者梗塞后室性心律失常Lown's分级<2组与Lown's分级≥2组比较，ACE基因型与等位基因频率均无显著差异（均P>0.05）。(3) 心肌梗塞组患者的年龄、体重指数、收缩压、舒张压、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、载脂蛋白AI、载脂蛋白B、脂蛋白(a)及血糖在ACE基因型间均无显著差异（均P>0.05）。结论：ACE基因多态性与心肌梗塞有关而与梗塞后室性心律失常的发生无关，ACE缺失多态性可能是中国汉族人心肌梗塞的独立危险因素。