Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure

BACKGROUND: Studies on the role of the angiotensin-converting enzyme (ACE) gene in the development of hypertension have yielded conflicting results. Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease. OBJECTIVE: To study the relationship between the ACE insertion/deletion (I/D) polymorphism, blood pressure and risk of hypertension in current, former and non-smokers in a population-based cohort. METHODS: We included 2412 non-smokers, 2794 former smokers and 1508 current smokers, all participants in the Rotterdam Study. In each group, we assessed the relationship between the ACE I/D polymorphism, systolic (SBP) and diastolic (DBP) blood pressures and risk of hypertension. Mean blood pressures and prevalence of hypertension were compared between carriers and non-carriers of the D allele. All analyses were adjusted for age, sex, body mass index, diabetes mellitus, high-density lipoprotein cholesterol, total cholesterol and use of antihypertensive medication. RESULTS: In non-smokers and former smokers, blood pressure and the risk of hypertension did not differ significantly between genotypes. In smokers, we found a significant increase in SBP in DD carriers (139.6 +/- 22.8 mmHg) compared with II carriers (136.0 +/- 22.7 mmHg) (P = 0.04). No effect of ACE genotype was observed for DBP. The risk of hypertension was significantly increased in smokers who carried one [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0 to 1.9; P = 0.05] or two (OR 1.5, 95% CI 1.1 to 2.2; P = 0.02) copies of the D allele. CONCLUSIONS: The D allele of the ACE polymorphism is associated with a significantly increased SBP and risk of hypertension in smokers. Our study underlines the importance of gene-environment interactions in the study of candidate genes for hypertension.     

Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism

Critical illness outcome may be causally related to inflammatory response severity. Given that tissue angiotensin-converting-enzyme (ACE) regulates such responses and that the deletion (D) [rather than insertion (I)] variant of the ACE gene is associated with higher tissue ACE levels, DD genotype might be associated with a poorer outcome in a uniform infectious disease state. Illness severity (Pediatric RIsk of Mortality score, the Glasgow Meningococcal Septicaemia Prognostic Score [GMSPS], and clinical course) was recorded for consecutive white patients with meningococcal disease (n = 110, 34 DD genotype, 61 male, aged 49.4 +/- 5.4 months) referred to the Royal Liverpool Children's Hospital, UK. Compared with children with > or = I allele, DD genotype was associated with 14% higher predicted risk of mortality (p = 0.038), higher GMSPS (DD 9.4 +/- 0.5, ID/II 7.7+/- 0.4 [mean +/- SEM], p = 0.013), greater prevalence of inotropic support (76% versus 55%, p = 0.03) and ventilation (82% versus 63%, p = 0.04), and longer Pediatric Intensive Care Unit (PICU) stay (5.8 versus 3.9, p = 0.02). DD genotype frequency was 6% (1 case) for the 18 children who did not require PICU care, 33% for the 84 PICU survivors, and 45% for those who died (p = 0.01). ACE DD is associated with increased illness severity in meningococcal disease.     

The relationship between angiotensin-converting enzyme insertion/deletion polymorphism and proliferative retinopathy in type 2 diabetes

A total of 136 type 2 diabetic patients with nonproliferative and 94 patients with proliferative diabetic retinopathy (PDR) without nephropathy were studied. The DD genotype of the angiotensin-converting enzyme polymorphism was more common in the PDR group (P < 0.001). In multivariate regression, the association remained significant (OR = 3.516).     

Association between angiotensin-converting enzyme insertion/deletion polymorphism and treatment response in type 2 diabetic patients

BACKGROUND: Our objective was to determine whether the angiotensin-converting enzyme insertion-deletion (ACE I/D) polymorphism affects the treatment responses in type 2 diabetic patients. METHODS: A total of 117 type 2 diabetic patients with poor metabolic control were evaluated and their treatment intensified before re-evaluation after a mean follow-up of 16.0 months. New insulin treatment was started in 61% of patients, the majority of whom used a combination of insulin and tablets. Earlier insulin treatment was continued and intensified for 9% of patients, and 19% of patients used oral treatment only. As antihypertensive treatment, 34% of patients used diuretics, 27% ACE-inhibitors, 38% beta-blockers and 21% calcium-channel blockers during the follow-up. For dyslipidemia, 6% of patients used fibrates and none used statins. RESULTS: There was a decrease in glycohemoglobin A1 levels [-2.0 (0.3) (S.E.) %], plasma total cholesterol [-0.2 (0.1) mmol/l] and plasma triglycerides [-1.2 (0.4) mmol/l], and an increase in plasma HDL cholesterol [0.07 (0.02) mmol/l] and weight [2.1 (0.5) kg] in response to intensified treatment. The changes in glycohemoglobin A1 (GHbA1) levels and HDL cholesterol were significantly associated with the ACE I/D polymorphism. The patients with the ACE I/I genotype had a greater decrease [-3.0 (0.7)] in their GHbA1 levels than the patients with I/D [-2.1 (0.5)] or D/D [-1.8 (0.4)] genotypes (P<0.03). HDL cholesterol levels increased more among the subjects homozygous for the I allele [0.21 (0.05)] than the I/D [0.04 (0.03)] or D/D [0.04 (0.03)] subjects (P<0.03). CONCLUSIONS: The results suggest that the ACE I/D polymorphism is associated with treatment responses in type 2 diabetic patients.     

Interaction of implantable defibrillator therapy with angiotensin-converting enzyme deletion/insertion polymorphism

INTRODUCTION: The angiotensin-converting enzyme deletion allele (ACE D) decreases survival in patients with advanced heart failure. Whether the adverse impact on survival reflects an increased risk of pump failure or arrhythmic sudden death remains uncertain. If the ACE D genotype increases the risk of sudden death, implantable cardioverter defibrillator (ICD) therapy should diminish its negative impact. We sought to evaluate the effect of ICD therapy on ACE D genetic risk. METHODS AND RESULTS: The Genetic Risk Assessment of Cardiac Events (GRACE) study enrolled 479 patients at the University of Pittsburgh between 1996 and 2001. Blood was genotyped for the ACE D/I (deletion/insertion) polymorphism. Of the 479 patients, 82 (77% male, 84% Caucasian, age 56 +/- 11 years, 60% ischemic, left ventricular ejection fraction 0.23 +/- 0.08) received an ICD and were selected for outcomes analysis (mean follow-up 871 +/- 538 days). Transplant-free survival and survival alone were compared in ACE DD patients (n = 24, 29%) versus ACE DI/II patients (n = 58, 71%). Survival was significantly improved in ACE DI/II patients compared to those without an ICD (1 year: 93% vs 87%; 2 year: 89% vs 77%; P = 0.02) but not in ACE DD patients. Transplant-free survival among patients with an ICD was significantly worse in ACE DD versus ACE DI/II (1 year: 67% vs 88%, 2 year: 55% vs 80%, P = 0.03). Analysis of survival as a single endpoint revealed a similar result (1 year = 78% vs 94%; 2 year: 72% vs 88%; P = 0.05). ICD telemetry data showed a nonsignificant trend toward fewer individuals with arrhythmias in the ACE-DD group (46% vs 65%, P = 0.22) CONCLUSION: ICDs do not diminish the adverse influence of the ACE DD genotype on survival. This finding suggests that mortality in this high-risk genetic subset of patients is due to progression of heart failure rather than arrhythmic sudden death.     

Lack of association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and vasospastic angina

Background and hypothesis: It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary atherosclerosis and myocardial infarction, but its relation to vasospastic angina has not been fully proven. In the present study, we investigated the possible relationship between the ACE I/D genotype and vasospastic angina. Methods: We explored the distribution of the ACE genotype in 20 patients with vasospastic angina without fixed coronary artery stenosis, 55 angina patients with fixed coronary artery stenosis, and 30 control subjects without coronary artery disease. Results: The frequency of the DD genotype in patients with vasospastic angina (DD: 30.0%, ID: 20.0%, II: 50.0%) did not differ from that in the control subjects (DD: 23.3%, ID: 26.7%, II: 50.0%), while the frequency in patients with coronary artery stenosis (DD: 43.7%, ID: 21.8%, II: 34.5%) was significantly higher than that in the control subjects. The frequency of the D allele also did not differ between patients with vasospastic angina (0.40) and control subjects (0.37), while the frequency was significantly higher in patients with coronary artery stenosis (0.55). Conclusions: These findings suggest that the ACE DD genotype is a potent genetic risk factor for organic coronary artery disease, while it confers no appreciable increase in risk of vasospastic angina. These results also suggest the diversity of the pathogenesis of vascular lesions in these two types of coronary artery disease.     

血管紧张素转换酶基因插入缺失多态性与心肺功能适应性的研究

目的探讨血管紧张素转换酶(ACE)插入/缺失(I/D)型等位基因与心肺功能适应性的关系。方法收集126名男性健康志愿者,分为体育锻炼组(锻炼组)65名,对照组61名,进行为期5年的前瞻性试验。锻炼组进行低中强度规律的体育锻炼,对照组不强求进行体育锻炼。试验时及以后每年进行踏车运动试验,测定有氧阈值等心肺功能适应性指标;用多聚酶链反应法分析ACE基因第16内含子I/D多态性。结果锻炼组有氧阈值试验前后分别为(14.4±3.9)ml·min-1·kg-1和(16.4±4.1)ml·min-1·kg-1,对照组分别为(14.2±3.6)ml·min-1·kg-1和(13.8±3.3)ml·min-1·kg-1,锻炼组试验前与试验后及对照组比较,差异有统计学意义(均为P<0.05);锻炼组II、ID、DD基因型者有氧阈值试验前分别为(13.6±4.1)ml·min-1·kg-1、(14.8±3.7)ml·min-1·kg-1和(14.7±3.8)ml·min-1·kg-1,试验后分别为(15.8±3.6)ml·min-1·kg-1、(17.2±4.6)ml·min-1·kg-1和(15.2±3.5)ml·min-1·kg-1,对照组分别为(13.8±2.9)ml·min-1·kg-1、(14.4±3.9)ml·min-1·kg-1和(13.9±4.1)ml·min-1·kg-1,试验后分别为(13.3±3.5)ml·min-1·kg-1、(14.4±3.3)ml·min-1·kg-1和(13.1±2.6)ml·min-1·kg-1,锻炼组II、ID基因型者试验前与试验后及对照组比较,差异有统计学意义(均为P<0.05),DD基因型者有氧阈值试验前与试验后及对照组比较,差异无统计学意义(均为P>0.05)。结论低中强度规律的体育锻炼能显著提高心肺功能;ACEII、ID基因型者较DD基因型者的心肺功能易通过体育锻炼而提高。     

原发性高血压患者血管紧张素转化酶基因多态性与血管内皮损伤的相关性

目的:探讨原发性高血压(EH)患者血管紧张素转化酶(ACE)基因I/D多态性与血管内皮损伤的相关性。方法:选择初次诊断的EH患者68例,采用聚合酶链反应(PCR)方法进行ACE基因分型,并测定其血浆可溶性P选择素(sP-selectin)、血栓烷B2(TxB2)和6-酮-前列腺素F1α(6-keto-PGF1α)浓度和血管假性血友病因子(v WF)抗原水平。结果:根据等位基因分布,EH患者分为DD型(18例)、ID型(26例)和II型(24例)3组;DD型的血浆sP-selectin、TxB2浓度和v WF抗原水平明显高于其他2型(P<0·05),而6-keto-PGF1α浓度则是DD型最低(P<0·05)。多因素Logistic回归分析显示ACE/DD基因型是引起患者血浆sP-selectin、TxB2、v WF升高和6-keto-PGF1α降低的独立危险因子。结论:ACE/DD基因型的EH患者较ACE/ID型和ACE/II型具有更为明显的血管内皮损伤倾向。     

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.     

Lack of association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and idiopathic dilated cardiomyopathy

Objectives. We sought to investigate the role of polymorphisms of the gene for angiotensin-converting enzyme in the development and progression of idiopathic dilated cardiomyopathy.

Background. Cardiovascular renin-angiotensin systems may be involved in cardiac remodeling and fibrosis. The absence (deletion [D]) of a 287-base pair marker in the angiotensin-converting enzyme gene (intron 16) is associated with increased serum angiotensin-converting enzyme levels. The DD genotype may be a risk factor for the development of end-stage heart failure due to cardiomyopathy. We therefore examined the relation of the angiotensin-converting enzyme genotype to idiopathic dilated cardiomyopathy and to markers of disease severity.

Methods. We studied 364 control subjects and 99 consecutive patients with idiopathic dilated cardiomyopathy. When the incidence of the DD genotype in our control group was assumed to be similar to that previously reported (27%), this study had a power of 0.9 to detect a different incidence in the patient group, if the true incidence in patients was 42%. Deoxyribonucleic acid (DNA) was isolated from blood samples, and angiotensin-converting enzyme genotype was determined by specific polymerase chain reaction and separation of amplified fragments by agarose gel electrophoresis. We also compared genotype distribution with that in previously reported European control subjects. Functional status, clinical course over a mean ± SD of 28 ± 33 months and outcome were documented. Cardiac morphology and function and evidence of rhythm disturbance were noninvasively determined.

Results. Angiotensin-converting enzyme genotype distribution and allele frequencies were similar in patients and control subjects to within 10% (with 95% confidence) and were also similar between patients and European control subjects. No markers of disease severity or progression other than duration of symptoms before diagnosis and the number of ventricular ectopic beats/h were significantly associated with the presence of the DD alleles.

Conclusions. We find no evidence to support an association between angiotensin-converting enzyme genotype and either the diagnosis of idiopathic dilated cardiomyopathy itself or progression of the disease.     

高血压合并脑梗死患者ACE基因I/D多态性分析

目的 探讨血管紧张素转换酶(ACE)基因插入／缺失(I／D)多态性与高血压合并脑梗死的关系。方法应用聚合酶链反应(PCR)方法检测54名正常人、40例高血压但无心脑血管合并症患和54例高血压合并脑梗死患的ACE基因型,同时检测血清ACE水平：结果 ACE基因I／D多态性与高血压无相关关系。与偶测血压、体重指数、血脂及载脂蛋白等临床、生化指标亦无相关关系,而与血清ACE活性显相关。高血压合并脑梗死组的ACED等位基因频率(66．7％)显高于高血压组(52．5％)和对照组(49．1％)：有高血压家族史的高血压合并脑梗死患的DD基因型频率(50．0％)及D等位基因频率(70．0％)显高于高血压组(23．1％,48．1％)和正常对照组(28．6％,51．2％)。结论 (1)ACED等位基因频率为高血压合并脑梗死的独立危险因素;(2)ACE基因缺失多态性与血清ACE活性有关,并增加高血压合并脑梗死的危险;(3)ACE基因缺失型可能为高血压合并脑梗死的遗传因素。     

Impact of maternal angiotensinogen M235T polymorphism and angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure, protein excretion and fetal outcome in pregnancy

OBJECTIVE: To test the hypothesis that genetically determined alterations of the renin-angiotensin system are associated with hypertensive disorders in pregnancy. METHODS: A genetic association study was conducted at the obstetrics department of the Charité university hospital, Berlin, Germany. A total of 1068 Caucasian women were consecutively included after delivery and genotyped for the angiotensinogen M235T polymorphism and the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism. RESULTS: Women homozygous for the angiotensinogen T allele have significantly elevated mean systolic and diastolic blood pressures in the third trimester (118.4 +/- 1.1/71.5 +/- 0.7 versus 116.9 +/- 0.3/70.4 +/- 0.2 mmHg, n = 128 versus 940; P < 0.05). This finding is especially pronounced in the subgroup of primigravid women. The ACE polymorphism is not associated with blood pressure during pregnancy. None of the polymorphisms is associated with urinary protein excretion or oedema during pregnancy. Maternal polymorphisms do not influence fetal growth and birth weight. There is, however, an interesting trend towards an increased incidence of circulatory system malformations in newborns carrying alleles that are known to be associated with decreased intrinsic renin-angiotensin system activity. CONCLUSION: We demonstrate for the first time in a large Caucasian population that a common maternal polymorphism of the angiotensinogen gene is related to a blood pressure increase during pregnancy. The angiotensinogen M235T polymorphism might contribute to the multifactorial pathogenesis of gestational hypertension and pre-eclampsia.     

Interaction between the angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea as a mechanism for hypertension

OBJECTIVE: Obstructive sleep apnoea (OSA) confers a risk of hypertension and cardiovascular complications. Both the renin-angiotensin-aldosterone system and OSA are important determinants of blood pressure, but it is not fully known how they interact. The aim of this study was to explore the interaction between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and OSA in the association with hypertension. DESIGN: A community-based, case-control design with hypertensive patients in primary care (n = 157) and normotensive population controls (n = 181). METHODS: All subjects underwent ambulatory polysomnography during one night. OSA was defined by a minimum of 10 apnoea/hypopnoea events per hour. Office blood pressure was measured and hypertension status was assessed. The genotypes were determined using polymerase chain reaction. RESULTS: An interaction analysis including sex, ACE I/D polymorphism (DD and ID versus II), and OSA identified a significant interaction between OSA and the ACE I/D polymorphism: odds ratio (OR) 6.3, 95% confidence interval (CI) 1.8-22.5, P = 0.004 as well as between OSA and sex: OR 3.3, 95% CI 1.1-9.6, P = 0.033. OSA was significantly associated with hypertension in men but not in women. CONCLUSION: The interaction between the ACE gene I/D polymorphism and OSA appears to be an important mechanism in the development of hypertension, particularly in men.     

Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene.

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.     

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the risk for restenosis after PTCA

The therapeutic benefit of percutaneous transluminal coronary angioplasty (PTCA) is limited by restenosis in about 30% of patients. The underlying mechanisms are currently not well understood. Besides clinical and angiographic variables, genetic factors may be involved. We determined the angiotensin I-converting enzyme (ACE) I/D genotype as a possible risk factor for restenosis in 511 consecutive patients who had undergone successful PTCA and follow-up angiography. Clinical and angiographic variables were also considered as possible predictors of restenosis. One hundred sixty patients had restenosis as defined by a greater than 50% progression of residual stenosis of the dilated segment at follow-up angiography. There were significantly more patients with the ACE DD genotype in the restenosis than in the no-restenosis group. This difference did not remain statistically significant in an analysis of covariance that included genetic and clinical variables. Patients who subsequently developed restenosis had a higher degree of stenosis and more severe lesions before PTCA as well as less residual stenosis immediately after PTCA. We conclude that the ACE DD genotype is not an independent risk factor for restenosis after PTCA.Presented in part at the 41st Annual Congress, International College of Angiology, Sapporo, Japan, July 1999.     

Insertion/deletion gene polymorphism of the angiotensin-converting enzyme and blood pressure changes in older adults. The Rotterdam study

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene may be involved in determining blood pressure changes. The aim of the present study was to assess the relationship between the ACE I/D gene and the change of blood pressure levels during follow-up. We calculated the difference between mean levels of SBP, DBP and PP obtained during the two observations as follows: BP mean levels obtained at third phase minus the BP mean levels at baseline and subsequently we investigated the association of the ACE I/D polymorphism and the mean changes of SBP, DBP and PP levels. The study was conducted within the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. Information on the II, ID and DD genotypes of the ACE gene and mean change of blood pressure levels were available in 3966 subjects. In adjusted models, subjects with the D allele had higher mean changes of systolic and pulse pressure (PP) than subjects with the I allele. The mean changes of systolic blood pressure were 6.1 (4.7-7.5), 8.2 (7.5-9.3) and 7.4 (5.9-8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The corresponding mean changes of PP through genotypes were 4.3 (3.3-5.4), 6.0 (5.3-6.7) and 5.9 (4.9-6.9) mm Hg, respectively. No difference was found for mean change of diastolic blood pressure among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with increased mean changes of systolic and PP.     

The relationship between angiotensin-converting enzyme (insertion/deletion) gene polymorphism and left ventricular remodeling in acute myocardial infarction

BACKGROUND: The development of left ventricular remodeling after acute myocardial infarction is a predictor of heart failure and mortality. The genetic influence on cardiac remodeling in the early period after acute myocardial infarction, is however, unclear. The aim ofthis study was to investigate the relationship between angiotensin-converting enzyme (ACE) gene polymorphism and left ventricular remodeling in the early period in patients with anterior myocardial infarction. METHOD: The study population consisted of 142 patients with their first attack of acute anterior myocardial infarction. Echocardiographic examinations were performed within 24 h of the first attack (first evaluation) and on the fifth day of acute myocardial infarction (second evaluation). Left ventricular end systolic and diastolic diameters, left ventricular end systolic and diastolic volumes, ejection fraction, mitral flow velocities (E, A, E/A), deceleration time, isovolumic relaxation time and myocardial performance index were calculated. ACE I/D polymorphism was determined using polymerase chain reaction amplification. RESULTS: On the basis of polymorphism of the ACE gene, the patients were classified into the three groups: group 1, deletion/deletion (n=59) genotype, group 2 insertion/deletion (n=69), and group 3 insertion/insertion (n=14) genotype. When the first and second sets of echocardiographic results of the groups were compared, all parameters were not different among three groups. In group analysis, Left ventricular systolic diameters, left ventricular diastolic diameters, left ventricular end diastolic diameters, left ventricular ejection fraction and myocardial performance index between first and second echocardiographic results were significantly different in deletion/deletion group and only myocardial performance index and left ventricular ejection fraction in insertion/deletion group (P<0.05). CONCLUSIONS: ACE gene polymorphism may influence early cardiac remodeling after acute myocardial infarction. Patients with the deletion/deletion-insertion/deletion genotype may be particularly more sensitive to ACE-I treatment possibly owing to the more prominent role of the renin-angiotensin system.     

The impact of the angiotensin-converting enzyme insertion/deletion polymorphism on severe hypoglycemia in Type 2 diabetes

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) is associated with altered serum ACE activity. Raised ACE levels and the ACE DD genotype are associated with a 3.2 to 6.8-fold increased risk of severe hypoglycemia in type 1 diabetes. This relationship has not been assessed in type 2 diabetes. We aimed to test for association of the ACE I/D polymorphism with severe hypoglycemia in type 2 diabetes. Patients with type 2 diabetes (n = 308), treated with insulin (n = 124) or sulphonylureas (n = 184), were classified according to whether or not they had previously experienced severe hypoglycemia. Samples of DNA were genotyped for the ACE I/D polymorphism using two alternative polymerase chain reactions to prevent mistyping due to preferential amplification of the D allele. Overall, 12% of patients had previously experienced one or more episodes of severe hypoglycemia. This proportion did not differ between genotype groups (odds ratio (95% confidence limits) for carriers of D allele relative to II homozygotes: 0.79 (0.35-1.78)). This study found no evidence for association of the ACE I/D polymorphism with severe hypoglycemia frequency in patients with type 2 diabetes. However, we cannot rule out a smaller effect (odds ratio 相似文献   

Linkage analysis of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and systemic lupus erythematosus

Previous studies have suggested an association between systemic lupus erythematosus (SLE) and an insertion/deletion polymorphism in the angiotensin-converting enzyme gene (ACE). This polymorphism consists of a 250-bp insertion/deletion of an alu repeat in the 16th intron of the ACE gene. Individuals homozygous for the deletion have a higher level of circulating enzyme. Due to the important role of this enzyme in regulating the renin--angiotensin and kallikrein--kininogen systems, it is possible that the ACE insertion/deletion may play a role in SLE, which can include vasculitis and vascular changes. Using primers flanking the insertion/deletion site, we have examined the ACE gene in lupus patients and family members using genomic DNA obtained from the Lupus Multiplex Registry and Repository (LMRR). We were unable to detect significant linkage or genetic association between the ACE gene and SLE.