血管紧张素转换酶和血管紧张素Ⅱ受体1A1166C基因多态性与脑出血的关系

目的探讨血管紧张素转换酶（ACE）基因插入/缺失多态性和血管紧张素Ⅱ受体1（AT1R）A1166C基因多态性与脑出血的关系,并分析两者是否有协同致脑出血的效应。方法应用聚合酶链反应及限制性片段长度多态性技术,检测80例脑出血患者（脑出血组）和90名健康对照者（健康对照组）的ACE和AT1R基因型和等位基因,并运用Logistic回归分析不同基因型致脑出血的效应。结果脑出血组ACEDD基因型频率为35.0%,D等位基因频率为51.9%,明显高于健康对照组的15.6%和38.9%,均P〈0.05;AT1RAC基因型频率为32.5%,C等位基因频率为16.2%,明显高于健康对照组的11.1%和5.6%,均P〈0.05;Logistic回归显示,170例入组者中,携带AT1RAC基因型（OR：3.852,95%CI：1.719～8.632;P〈0.01）、ACE基因DD型（OR：2.923;95%CI：1.406～6.079;P〈0.01）及同时携带有AT1RAC基因型和ACEDD基因型（OR：4.250;95%CI：1.479～12.209;P〈0.01）是脑出血的独立危险因素。结论ACE基因插入/缺失多态性和AT1RA1166C基因多态性可能是脑出血发病的独立遗传因素;且两者间具有协同致脑出血的作用。     

血管紧张素转换酶和血管紧张素受体基因多态性与冠心病的关系

目的　探讨深圳地区冠心病 (CAD)与血管紧张素转换酶 (ACE)基因与血管紧张素 的 1型受体 (AT1R)基因多态性的关系。方法　分别采用 PCR及 PCR- Afl II酶切法 ,检测 89例 CAD患者和 14 8例健康对照的 ACE和AT1R基因型。结果　 CAD组与对照组比较 ,ACE DD基因型频率 (2 4 .7%比 8.1% ,P<0 .0 1)及 D型等位基因频率 (4 4 .4 %比 33.4 % ,P<0 .0 5 )均为升高。 CAD组与对照组 AT1R基因型频率分布无显著性差异 (P>0 .0 5 )。携带 AT1R C等位基因的个体患 CAD的风险与其同时携带 ACE DD基因型无关 (P>0 .0 5 )。结论　深圳地区CAD的发生和发展可能与 ACE基因 I/ D多态性有关 ,而与 AT1R基因 A116 6 C多态性无关     

原发性高血压并发脑梗死患者血管紧张素转换酶和血管紧张素受体基因多态性的研究

目的 :探讨血管紧张素转换酶 (ACE)基因及血管紧张素Ⅱ 1型受体 (AT1R)基因A116 6 /C多态性与原发性高血压 (EH)及其并发脑梗死的关系。方法 :应用聚合酶链反应及PCR加酶解方法检测 15 0例健康者 (对照组 )及 15 2例EH无并发症患者 (EH组 )和 80例EH并发脑梗死患者 (EH并发脑梗死组 )ACEI/D基因多态性的ACE及AT1RA116 6C突变。结果 :EH组及EH并发脑梗死组的ACE基因的D等位基因频率为 5 0 %及 4 8% ,明显高于对照组的 33% (P <0 .0 5 )。AT1R基因的C等位基因频率在 3组之间差异无显著性意义 (P >0 .0 5 )。结论 :ACE基因可能是EH及EH并发脑梗死的重要遗传因素 ,而AT1R基因与EH发病及EH患者是否易患脑梗死无关     

原发性高血压患者血管紧张素转化酶和血管紧张素受体基因多态性的研究

目的　探讨血管紧张素转化酶 ( ACE)及血管紧张素 - 1型受体 ( AT1 R)基因多态性与原发性高血压 ( EHT)的关系。方法　应用聚合酶链反应及 PCR加酶解方法检测 1 50例健康人 ( NT)及 1 52例 EHT患者 ACE I/ D基因多态性的 ACE及 AT1 R A1 1 6 6 C突变。结果　 EHT组ACE I/ D基因多态性等位基因频率 I为 0 .50 ,D为 0 .50 ,D等位基因频率及基因型频率显著高于 NT组 ( P<0 .0 5) ;而两者之间的 AT1 R A1 1 6 6 C的C等位基因频率差异无显著性 ( P>0 .0 5)。结论　 ACE基因可能是 EHT的重要遗传因素 ,AT1 R基因 A1 1 6 6 C多态性与 EHT无关     

The renin-angiotensin system genetic polymorphisms and rheumatic mitral valve disease

BACKGROUND AND AIM OF THE STUDY: Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, angiotensinogen (AGT) gene polymorphism and angiotensin II type 1 receptor (AT1R) polymorphism in relation to rheumatic mitral valve disease were examined in a case-control study to investigate possible relationships between these gene polymorphisms and rheumatic mitral valve disease in patients undergoing mitral valve replacement (MVR). METHODS: A total of 50 patients with rheumatic mitral valve disease and undergoing MVR was compared with 50 normal, and age- and sex-matched control subjects. ACE I/D, AGT gene M235T and AT1R-adenine/cytosine 1166 (A1166C) genotype polymorphisms were identified by polymerase chain reaction (PCR) -based restriction analysis. RESULTS: ACE I/D polymorphism differed significantly between the groups. The control group mostly represented the heterozygote ID allele (74%), while the MVR group showed frequencies of 60% for the homozygote DD and II alleles. MM homozygote frequency was significantly greater in controls, but TT homozygote frequency was significantly greater in the MVR group. AT1R-A1166C genotype polymorphism also differed significantly between groups; the MVR group had 73.7% of the AC heterozygote allele, while controls had 64.4% of the AA and 66.7% of the CC homozygote alleles. CONCLUSION: These results provided evidence of an association between ACE I/D polymorphism, M235T polymorphism and AT1R-A1166C genotype polymorphism and rheumatic mitral valve disease.     

Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC?+?CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p?<?0.0001, OR?=?4.9, 95% CI?=?2.7–8.8; p ? 0.0001, OR?=?3.6, 95% CI?=?2.2–5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC?+?CC) genotypes and C-allele compared with controls (p ? 0.0001, OR?=?5.1, 95% CI?=?2.7–9.7; p ? 0.0001, OR?=?3.5, 95% CI?=?2.1–6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p ? 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.     

ACE and TGFBR1 genes interact in influencing the susceptibility to abdominal aortic aneurysm

A role of ACE I/D polymorphism in the pathogenesis of abdominal aortic aneurysm (AAA) has been demonstrated, possibly due to the effect of angiotensin II on vascular tissue remodelling. Angiotensin II exerts profibrogenic effects through the local induction of TGF-beta. Dysregulated TGF-beta signalling may result from mutations in TGFBR1 and TGFBR2 genes, thus resulting in degenerative changes in the vessel wall. We performed a case-control study in order to investigate the role of TGFBR1 9A6A polymorphism as predisposing factor to AAA per se, and in the presence of ACE DD and AT1R 1166 CC genotypes in 201 AAA patients (mean age+/-S.D., 71.5+/-6.9) referred to the Unit of Vascular Surgery of the University of Florence, compared with 252 healthy controls (mean age+/-S.D., 70.6+/-8.6). A significant difference in genotype distribution and allele frequency between patients and controls was found for ACE, but not for AT1R and TGFBR1 polymorphisms. At univariate analysis a significant association between ACE DD, but not AT1R CC and TGFBR1 6A allele, and the susceptibility to the disease was found [ACE DD OR=1.86 (95% CI 1.26-2.76), p=0.002]. After adjustment for age, gender, traditional cardiovascular risk factors, and CAD, PAD and CVD, ACE DD genotype still affected the susceptibility to AAA [OR=2.13 (95% CI 1.06-4.28), p=0.03], and the contemporary presence of ACE DD genotype and TGFBR1 6A allele, increased the predisposition to the disease [OR=5.09 (95% CI 1.44-18.02), p=0.01]. This study, which demonstrates an interaction between ACE and TGFBR1 genes in predisposing to AAA, may provide further information on the mechanisms contributing to AAA susceptibility, and offer a topic for future larger studies.     

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.     

The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI). DESIGN AND METHODS: Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues. RESULTS: In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P=0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolaemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR=0.743, 95% CI=0.595-0.927, P=0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P=0.856), or in multivariate analysis adjusted for the same confounders (RR=0.743, 95% CI=0.473-1.167, P=0.197). CONCLUSIONS: Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.     

Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias

OBJECTIVES: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. METHODS: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. RESULTS: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. CONCLUSIONS: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.     

Population-based case-control study of renin-angiotensin system genes polymorphisms and hypertension among Hispanics.

The effect of polymorphisms of the RAS genes on the incidence of hypertension seems to be population-dependent. We studied the effects of the angiotensinogen T174M and M235T, angiotensin converting enzyme insertion/deletion (ACE I/D), and angiotensin II receptor 1 (AT1R) A1166C gene polymorphisms on the risk of hypertension among Hispanics. We selected all cases (n=256) and 257 age and sex group-matched controls from a random sample of free living Colombians (n=2,989). Logistic regression was used to estimate the independent effect of each polymorphism. All polymorphisms were in Hardy-Weinberg equilibrium in controls, with the exception of M235T, which showed a small excess of heterozygotes (p=0.005; disequilibrium coefficient, D=-0.0264). After adjustment for age, sex, body mass index, race, physical activity, family history of hypertension and cardiovascular disease, and other polymorphisms, subjects with the ACE DD genotype were 1.56 times (95% confidence interval [CI]: 1.05, 2.33) more likely to be hypertensive than carriers of the I allele (p=0.03). Also, adjusted systolic and diastolic blood pressure were 4.58 (95% CI: -0.39, 9.56) and 3.32 (95% CI: 0.78, 5.86) mmHg higher in DD homozygous individuals than in carriers of the I allele, respectively. Approximately 15% of the cases of hypertension in this population could be attributed to carriage of the DD genotype. None of the other polymorphisms was associated with either hypertension or blood pressure level. In conclusion, the ACE DD genotype appears to be an independent risk factor for development of hypertension and may explain a significant fraction of incident cases among Hispanics.     

Angiotensin-converting enzyme DD genotype, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase first-trimester fetal-loss susceptibility.

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evaluated the angiotensin converting enzyme (ACE) and the angiotensin type 1 receptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as possible risk factors for fetal loss. Fifty-nine women with a history of three or more first-trimester fetal losses and 70 healthy women with a history of normal pregnancies were enrolled in this study. Thrombophilic factors, ACE insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G20210A and factor V Leiden mutations were analyzed. At univariate and multivariate analysis, a significant association between ACE DD and AT1R CC genotype and fetal loss was observed. The effect of the ACE DD genotype on the risk of fetal loss was higher in AT1R C allele carriers. The prevalence of hyperhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 95% percentile; cut-off, 10.5 micromol/l per l) was significantly higher in women with fetal loss, and an association between Hcy and fetal loss was detected. All patients showed normal antithrombin, protein C, protein S, and plasminogen activator inhibitor-1 (PAI-1) values. The presence of one risk factor not associated with others was found in 33 out of 59 patients (56%); ACE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hcy. Large-scale studies are warranted to attribute clinical relevance to these polymorphisms as risk factors for complicated pregnancies.     

ACE基因I／D、AT1R基因A1166C多态性与奥美沙坦酯降压作用的关系

目的探讨血管紧张素转换酶（ACE）基因I／D、血管紧张素Ⅱ-1型受体（ATlR）基因A1166C多态性与奥美沙坦酯降压作用的关系。方法76例轻、中度高血压（EH）患者服用奥美沙坦酯治疗8周;用聚合酶链式反应一限制性片段长度多态性对其血白细胞基因组DNA肾索-血管紧张素-醛固酮系统基因多态性位点ACEI／D、ATlRA1166C基因型进行检测。结果ACE基因含D等位基因患者的SBP、DBP、脉压降幅及降压总有效率均高于含I等位基因者,DD＋AA基因型患者的SBP降幅高于DD＋AC基因型者（P均〈0．05）。结论ACE基因含D等位基因EH患者对奥美沙坦酯降压治疗敏感;ACE、AT1R基因联合作用可能影响奥美沙坦酯的降压疗效。     

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.     

Relation between the insertion/deletion polymorphism of the angiotensin I converting enzyme gene and restenosis after coronary stenting

BACKGROUND: Observations with intravascular ultrasound demonstrated that neointimal hyperplasia is the predominant factor responsible for in-stent restenosis. Experimental data suggest that angiotensin I converting enzyme (ACE) plays a role in the thickening of neointima after balloon denudation. Insertion/deletion (I/D) polymorphism of the ACE gene is significantly associated with plasma level of ACE and subjects with D/D genotype have significantly higher plasma levels of ACE than normal. OBJECTIVE: To investigate whether this polymorphism influences the risk of restenosis after coronary stenting. METHODS: We genotyped 158 patients who had undergone single-vessel coronary stenting for the ACE I/D polymorphism. RESULTS: Of the 158 patients, 56 (35%) had the D/D genotype, 71 (45%) had the I/D genotype and 31 (20%) had the I/I genotype. Prevalences of genotypes were compatible with Hardy-Weinberg equilibrium and distributions of ACE genotype among patients and 132 healthy controls from the same geographic area did not differ. At follow-up (after a median duration of 5.4 months), overall rates of angiographic restenosis and of revascularization of target lesion (RTL) were 32.3 and 22.8%, respectively. Of 51 patients with angiographic restenosis, 31 (60.8%) had focal and 20 (39.2%) had diffuse patterns of restenosis. Diffuse in-stent restenosis was significantly more prevalent among patients with D/D genotype (P = 0.016). Multiple stepwise logistic regression analysis identified ACE I/D polymorphism as the independent predictor of angiographic restenosis and RTL. Relative risk of angiographic restenosis was 6.29 [95% confidence interval (CI), 1.80-22.05, P = 0.0004] for D/D genotype and 3.88 (95% CI 1.11-13.12, P = 0.029) for I/D genotype, whereas relative risk of RTL was 7.44 (95% CI 1.60-34.58, P = 0.01) for D/D genotype and 3.88 (95% CI 0.083-18.15, P = 0.085) for I/D genotype. CONCLUSIONS: The ACE I/D polymorphism is significantly associated with risk of angiographic and clinical restenosis after coronary stenting. Angiographic pattern of restenosis is also significantly associated with I/D polymorphism, diffuse type being more prevalent among subjects with D/D genotype.     

血管紧张素Ⅱ 1型受体基因573T〉C和1166A〉C多态性与新疆哈萨克族高血压的关系

目的:研究血管紧张素Ⅱ 1型受体(AT1R)基因573T>C和1166A>C多态性与新疆哈萨克族原发性高血压(EH)的关系.方法:采用病例-对照研究随机选取新疆哈萨克族牧民EH患者(EH组)194例,正常血压者(对照组)115例,采用聚合酶链反应和限制性片段长度多态性技术检测AT1R基因573T>C和1166A>C多态性,用最大似然法估计两位点单体型频率.结果:AT1R基因573T>C多态性在EH组中T、C等位基因频率分别为0.799,0.201,对照组中T、C等位基因频率分别为0.713和0.287,EH组T等位基因频率高于对照组(P<0.05).1166A>C位点仅在EH组检测到1例CC基因型,A、C 2种等位基因和基因型频率在2组间分布差异无统计学意义(均P>0.05).573T>C和1166A>C间未检测到连锁不平衡.T573-A1166组成的单体型频率最高,占70.4%,其次是C573-A1166,为17.1%.2组间单体型分布差异无统计学意义(P>0.05).不同单体型对EH的影响差异无统计学意义(均P>0.05).结论:AT1R基因573T>C的T等位基因和TT及TC基因型是新疆哈萨克族EH可能的易感因素,而573T>C和1166A>C组成的单体型可能与新疆哈萨克族EH无关.     

血管紧张素Ⅱ1型受体基因多态性与高龄原发性高血压的相关性

目的研究血管紧张素Ⅱ1型受体(AT1R)基因A1166C多态性与汉族高龄原发性高血压的相关关系。方法采用PCR-RFLP方法,对山东省章丘地区高龄原发性高血压患者104例(高龄高血压组)和体检正常老年人98例(正常对照组)的外周血白细胞DNA,进行AT1R基因A1166C多态性检测,观察AA、AC和CC不同基因型以及该点A、C不同等位基因频率在两组中的分布。结果AA、AC和CC基因型在高龄高血压组的分布为83(79.81%)、20(19.23%)和1(0.96%),正常对照组为82(83.67%)、16(16.33%)和0,两组比较差异无显著性意义(χ2=0.50,P>0.05);A1166与C1166等位基因频率在高龄高血压组中分别为186(89.42%)和22(10.58%),正常对照组为180(91.84%)和16(8.16%),两组比较差异无显著性意义(χ2=1.38,P>0.05)。结论AT1R基因A1166C分子变异与山东省章丘地区汉族高龄原发性高血压无相关性。     

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity

OBJECTIVES: We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function. BACKGROUND: The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene. METHODS: In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-NG monomethyl arginine. RESULTS: Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 +/- 26% vs. 121 +/- 11%, p = 0.003, and diameter increase 21.9 +/- 2% vs. 17 +/- 1%, p = 0.03, ACE II vs. DD, respectively). L-NG monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow -10 +/- 4% vs. 11 +/- 5%, p = 0.003, ACE DD vs. II and diameter constriction -6.3 +/- 1.2% vs. -1.9 +/- 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH. CONCLUSIONS: Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.     

A/C1166 gene polymorphism of the angiotensin II type 1 receptor (AT1) and ambulatory blood pressure: the Ohasama Study.

We previously investigated the relation between hypertension and each of three major genetic polymorphisms in the renin-angiotensin (AGT)-aldosterone system (R-A-A), AGT M235T, angiotensin convert enzyme (ACE) I/D, and CYP11B2 -344C/T, by means of ambulatory blood pressure (ABP) monitoring in a general Japanese population (the Ohasama Study). A/C1166 gene polymorphism in the 3' untranslated region of the angiotensin II type 1 receptor (AT1) gene is the final remaining major target in R-A-A to be examined in the Ohasama Study population. In the present study, the AT1 A/C1166 polymorphism was genotyped by the TaqMan polymerase chain reaction (PCR) method or restriction fragment length polymorphism (RFLP) in 802 Japanese subjects aged 40 and over, who were previously genotyped for the AGT M235T, ACE D/I, CYP11B2 -344C/T polymorphisms. The AA genotype, AC genotype, and CC genotype were present in 678 (84.5%), 121 (15.1%), and 3 (0.4%) of subjects, respectively. Since the frequency of the C allele was quite low (0.079), the genotypes were classified according to the presence or absence of the C allele. Although daytime blood pressure (BP) was higher in subjects with the C allele, the difference was not statistically significant after adjusting for age, gender, body mass index, and smoking status. No significant difference was noted in the prevalence of cardiovascular diseases or nocturnal BP decline between the two groups. These results indicated that AT1 A/C1166 polymorphism was not associated with any clinical parameters associated with hypertension or atherosclerosis in the Japanese population.     

Association between A/C1166 gene polymorphism of the angiotensin II type 1 receptor and biventricular functions in patients with acute myocardial infarction.

BACKGROUND: Although there have been several association studies of angiotensin II type 1 receptor (AT1R, A/C1166) gene polymorphism in clinical endpoints such as myocardial infarction (MI), hypertension, aortic stiffness, and left ventricular mass, the relationship between AT1R polymorphism and biventricular function in acute anterior MI has not been studied before. METHODS AND RESULTS: The study group comprised 132 consecutive patients who were admitted to the coronary care unit with their first acute anterior MI. Systolic and diastolic diameters, volumes, inflow properties, ejection fraction and myocardial performance index of both ventricles were measured. AT1R polymorphism was determined using polymerase chain reaction amplification. Based on A/C1166 polymorphism of AT1R, the patients were classified into 3 groups: group 1, A/A (n=91) genotype, group 2 A/C (n=28), and group 3 C/C (n=13) genotype. When the left ventricular and right ventricular echocardiographic functions were compared, all parameters of the 3 groups were found to be similar. No difference was detected in either the genotype distribution or allele frequencies between the patients and the controls for AT1R. CONCLUSIONS: The results suggest that A/C1166 polymorphism of AT1R did not influence the risk of either acute MI or biventricular function after anterior MI.