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.     

DD angiotensin-converting enzyme gene polymorphism is associated with endothelial dysfunction in normal humans.

A polymorphism within the angiotensin-converting enzyme (ACE) gene may increase the risk of myocardial infarction in individuals previously thought to be at low cardiovascular risk. The mechanism through which it exerts this effect is unknown but may be due to increased angiotensin II-induced nitric oxide (NO) breakdown and/or reduced bradykinin-mediated NO release. We investigated whether endothelial function was different between different ACE genotypes. We performed a cross-sectional study comparing the endothelial function of the 3 genotypes (II: n=25; ID: n=31; DD: n=12). Mean+/-SD ages of the subjects were 24+/-4 (II), 25+/-6 (ID), and 25+/-6 (DD) years. We assessed the impact of the genotypes on endothelial function and found that the DD genotype was associated with a significant blunting in endothelial-dependent vasodilatation (forearm blood flow data are presented as mean+/-SD ratio of blood flow in response to 3 incrementally increasing doses of each vasoactive agent in the test arm to blood flow in the control arm; the comparison is between DD versus ID versus II; the P value is an expression of an overall difference by ANOVA, and the 95% CIs are of a pairwise comparison between genotypes): acetylcholine, 2.88+/-1.45 versus 3.81+/-1.93 versus 4.23+/-2.37 (P=0.002; 95% CI [II versus ID], -0.19 to 0.91; 95% CI [II versus DD], 0.36 to 1.80; 95% CI [ID versus DD], 0.02 to 1.42). There was also a significant difference with the endothelial-independent vasodilator sodium nitroprusside, with values of 2.11+/-1.00 versus 2.55+/-1.36 versus 2.75+/-1.18 (P<0.05; 95% CI [II versus ID], -0.15 to 0.51; 95% CI [II versus DD], 0.03 to 0.89; 95% CI [ID versus DD], -0.13 to 0.71), but not with verapamil. There was no effect of the ACE genotype on endothelial-dependent or -independent vasoconstrictors NG-monomethyl-L-arginine or norepinephrine. Investigating the effects of cigarette smoking on each genotype demonstrated that for II and DD genotypes, acetylcholine responses were further blunted if subjects smoked. These data demonstrate that the DD ACE genotype in a young population is associated with a blunting of stimulated endothelial NO and donated NO responses but not to non-NO vasodilators or vasoconstrictors.     

Carotid and femoral artery stiffness in relation to three candidate genes in a white population

Different genetic polymorphisms influence cardiovascular disease. We recently discovered a relationship between the intima-media thickness of the muscular femoral artery, but not the elastic common carotid artery, and the combined ACE (ACE, I/D), alpha-adducin (Gly460Trp),and aldosterone synthase (AS, C-344T) gene polymorphisms. To investigate the relationship between these polymorphisms and functional properties of the carotid artery and femoral artery, a sample of 756 subjects enrolled in a population study were genotyped for the presence of the ACE D, alpha-adducin 460Trp, and aldosterone synthase -344T alleles. Vessel wall properties were assessed using a vessel wall movement detector system in combination with applanation tonometry. Statistical analysis allowed for confounders and interaction among genes. Cross-sectional compliance of the common carotid artery was negatively associated with the ACE D allele. ACE II versus ACE DD homozygotes differed, expressed as a percentage of the population mean (7.0%; 95% confidence interval [CI], 1.6% to 12.4%; P=0.02). In multigene analysis, ACE DD subjects also deviated significantly from the population mean for the distensibility coefficient of the common carotid artery when carrying the AS/T allele (-5.5%; 95% CI, -9.3% to -1.7%; P<0.01), without a change in cross-sectional compliance. ACE DD subjects, when homozygote for alpha-adducin Gly460, had a lower femoral cross-sectional compliance (-10.4%; 95% CI, -1.9% to -18.9%; P<0.03) and a lower distensibility (-9.7%; 95% CI, -2.1% to -17.3%; P<0.02) compared with the population mean. These data show that functional large artery properties are influenced by the ACE I/D polymorphism. Cross-sectional compliance and distensibility coefficients are influenced by the ACE I/D genotype, but this influence depends on the vascular territory and genetic background.     

Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations. Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion/ deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement. We evaluated vascular involvement by the presence or absence of hypertension, Raynaud's phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynaud's phenomenon compared to those without Raynaud's phenomenon (P = 0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43-5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12-0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P = 0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05-0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID= 34.5+/-10.8, II + DD = 25.6+/-10.2, P= 0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7+/-8.4, ID+DD=21.3+/-9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P = 0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynaud's phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynaud's phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.     

Angiotensin-converting enzyme gene polymorphism influences degree of left ventricular hypertrophy and its regression in patients undergoing operation for aortic stenosis.

Insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in patients with cardiomyopathy and congestive heart failure. Patients with aortic stenosis (AS) have varying degrees of LVH at a given valve area. The aim of this study was to examine the relation between ACE gene polymorphism and the degree of LVH in patients undergoing operation for AS. Eighty-two patients who underwent operation for AS with a stentless valve were followed prospectively with echocardiographic assessments of left ventricular mass index (LVMI). ACE gene polymorphism was determined by polymerase chain reaction. The genotype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aortic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197 +/- 47 g/m2) preoperatively than those with ID (175 +/- 41 g/m2) or II (155 +/- 43 g/m2) genotypes (p = 0.01). LVMI decreased significantly in DD (p <0.001) and ID (p <0.001) genotypes but not in the II genotype during follow-up (mean 15 months). There was a significant difference in regression of LVMI over time between genotypes (p = 0.0056), with no significant difference between genotypes at follow-up. The DD genotype of the ACE gene is associated with increased preoperative LVH in patients treated surgically for AS. The DD genotype appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload.     

Impaired fasting glucose is associated with increased arterial stiffness in elderly people without diabetes mellitus: the Rotterdam Study

OBJECTIVES: To study the association between impaired fasting glucose (IFG) and arterial stiffness in older adults. DESIGN: Cross-sectional population-based study. SETTING: The Rotterdam Study, a Dutch population-based cohort study. PARTICIPANTS: Two thousand nine hundred eighty-seven subjects aged 60 and older. MEASUREMENTS: Arterial stiffness assessed by measuring common carotid arterial distensibility and glucose status classified into three categories: normal fasting glucose (NFG) (fasting glucose <6.1 mmol/L), IFG (fasting glucose 6.1-6.9 mmol/L), and diabetes mellitus (DM). RESULTS: In the total cohort, common carotid distensibility decreased with increasing impairment of glucose metabolism. Subjects younger than 75 with IFG were comparable with subjects with NFG with respect to arterial stiffness. Subjects aged 75 and older with IFG had stiffer arteries than subjects with NFG, reaching the same arterial stiffness as subjects with DM. For subjects younger than 75, mean difference in distensibility coefficient between subjects with NFG and with IFG was 0.1 (95% confidence interval (CI)=-0.04-0.05, P=.88) and between subjects with NFG and with DM was 1.2 (95% CI=0.7-1.7, P<.001). For subjects aged 75 and older, the mean difference between these groups was 0.7 (95% CI=0.2-1.2, P=.007) and 0.8 (0.3-1.4; P=.002), respectively. In the total cohort, fasting glucose was strongly associated with carotid distensibility (beta-coefficient=-0.29, P<.001). CONCLUSION: IFG is related to arterial stiffness in elderly subjects. An advanced stage of arterial stiffness, comparable with that of subjects with DM, is only reached at the age of 75.     

The association between angiotensin-converting enzyme gene polymorphism and coronary calcification. The Rotterdam Coronary Calcification Study

BACKGROUND: An insertion/deletion (I/D) polymorphism in the gene encoding angiotensin-converting enzyme (ACE) has been associated with serum ACE levels. The association between the ACE I/D polymorphism and coronary heart disease is unclear. Electron-beam-computed tomography (EBT) is a technique to non-invasively quantify the amount of coronary calcification. We investigated the association between the ACE I/D polymorphism and coronary calcification. METHODS AND RESULTS: The Rotterdam Coronary Calcification Study is a population-based study in subjects aged 55 years and over. EBT scanning was performed in 2013 participants. Coronary calcification was quantified according to the Agatston score. The ACE I/D polymorphism was available for 1976 subjects. Geometric mean calcium scores in men with the II, ID and DD genotype were 167, 207 and 219, respectively. However, the difference in calcium score (p=0.19 for ID versus II; p=0.15 for DD versus II) and the trend (ptrend=0.17) were not significant. Calcium scores in women with the II, ID and DD genotype were 44, 42 and 36, respectively. There were no significant differences in calcium score (p=0.78 for ID versus II; p=0.29 for DD versus II), neither was the trend (ptrend=0.27). After we stratified on cardiovascular risk factors, no associations were present. CONCLUSION: The present study failed to show an association between the ACE I/D polymorphism and coronary calcification in the general population. Also, no significant associations were present between the ACE I/D polymorphism and coronary calcification in strata of cardiovascular risk factors.     

Deletion Polymorphism of Angiotensin-Converting Enzyme Gene and Left Ventricular Hypertrophy in Southern Italian Patients

Objectives. This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI).Background. The renin–angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy.Methods. The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient.Results. Left ventricular mass index values (mean ± SD) were 137 ± 28 g/m²in patients with the DD genotype, 125 ± 27 g/m²in those with the ID genotype and 115 ± 27 g/m²in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02).Conclusions. Our data show that the LVMI was significantly enhanced in patients with the DD genotype.(J Am Coll Cardiol 1997;29:365–9)     

An interaction between systolic blood pressure and angiotensin-converting enzyme gene polymorphism on carotid atherosclerosis.

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE activity, with the D allele being associated with higher ACE levels than the I allele. Thus, chronic exposure to high levels of circulating and tissue ACE may well predispose to vascular wall thickening and atherosclerosis. However, the effect of the ACE gene on carotid atherosclerosis remains controversial. We investigated the association between ACE gene I/D polymorphism and risk factor-dependent augmentation of carotid arterial remodeling in subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid artery with intima-media thickness (IMT) by ultrasonography in 184 patients (mean age +/- SD, 67 +/- 14 years old) and studied whether any risk factor-gene interactions were associated with carotid atherosclerosis. Out of the 184 subjects, 71 had the ACE II genotype, 87 the ID genotype and 26 the DD genotype. There was no significant difference in IMT among the three ACE genotypes. In total subjects, multiple regression analysis showed that age, total-cholesterol (T-C), and HDL-cholesterol (HDL-C) were significantly associated with IMT. However, the association between risk factors and IMT was genotype-specific. Systolic blood pressure (SBP) and HDL-C were significantly associated with IMT in ACE D carriers (DD+ID), but not in subjects with the ACE II genotype. Similarly, T-C was significantly associated with IMT only in subjects with the ACE II genotype. A general linear model of the interaction between the ACE genotype and the conventional risk factors showed that the SBP-ACE genotype interaction were significantly associated with IMT (F = 7.915; p = 0.005). This finding further supports the idea that analysis of risk factor-gene interaction could be a useful tool for deriving specific predictive information about the development of atherosclerosis.     

血管紧张素转化酶基因多态性对血清血管紧张素转化酶水平及血脂的影响

为探讨血管紧张素转化酶基因多态性对本地人群高血压患者和正常人血清血管紧张素转化酶及血脂水平的影响,采用聚合酶链反应技术,对118例高血压患者和98例正常人的血管紧张素转化酶基因插入/缺失多态性进行分型,并检测血清血管祭张素转化酶活性及血脂含量。结果发现,高血压组血管紧张素转化酶三种基因型(缺失纯合子型、插入纯合子型和杂合子型)及插入/缺失等位基因的频率与正常对照组比较差异无统计学意义(X2=0.468,P=0.791;X2=0.379,P=0.538)。血清血管紧张素转化酶活性在三种基因型之间差异有显著性意义(F=17.107,P=0.000)。高血压组总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)高于正常对照组(P<0.05);高血压组三种基因型之间血脂各指标含量及正常对照组三种基因型之间总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和载脂蛋白B含量差异有显著性意义(P<0.05)。此结果提示,血管紧张素转化酶基因多态性与血清血管肾张素转化酶活性及血脂含量有关,缺失纯合子型高血压患者血清血管紧张素转化酶活性最高且易患高脂血症。     

Angiotensin-converting enzyme gene polymorphism in a cohort of coronary angiography patients

An association between a polymorphism of the angiotensin-converting enzyme (ACE) gene and myocardial infarction (MI) in men has been previously reported. The present study examines the association between ACE genotype, atherosclerosis, MI, hypertension and other cardiovascular risk factors in Caucasian men (n=576) and women (n=124) who have undergone coronary angiography. Gene frequencies are also reported for African-American men (n=56). Genotype determination was based on the presence (allele I) or absence (allele D) of a 287 nucleotide Alu sequence in intron 16 of the ACE gene. Genotype frequencies for DD, ID and II were: 30.9, 47.7, 21.4% for Caucasian men; 28.2, 48.4, 23.4% for Caucasian women; and 30.4, 46.4, 23.2% for African-American men. There were no statistically significant associations between ACE genotype and number of plaques (> or =10% obstruction), lipid variables, or body mass index (BMI) for Caucasian men. Caucasian women with the DD genotype had on average fewer plaques, but this was accounted for by their younger ages. In Caucasian males, the DD genotype independently contributed to the presence of hypertension (odds ratio=1.8, 95% CI 1.1-2.9) after adjusting for age and BMI. In Caucasian males with total cholesterol levels less than 200 mg/dl (n=237), the DD (odds ratio=2.5, 95% CI 1.2-5.4) and ID genotypes (odds ratio=2.2, 95% CI 1.1-4.4) were associated with a history of MI.     

Relationship between polymorphism of the angiotensin-converting enzyme gene and the response to angiotensin-converting enzyme inhibition in hypertensive patients.

The aim of this study was to investigate the relationship between polymorphism of the anglotensin-converting enzyme (ACE) gene and the blood pressure response to ACE inhibition in a hypertensive cohort. Imidapril (5-10 mg/day) or benazepril (10-20 mg/day) was administered for 6 weeks to 517 essential hypertensives. ACE gene polymorphism was examined by the polymerase chain reaction (PCR) method and the patients were classified as having the 190-bp deletion homozygous (DD) genotype, the 490-bp insertion homozygous (II) genotype, or the 490-bp insertion, 190-bp deletion heterozygous (ID) genotype. The achieved change in systolic and diastolic blood pressure (SBP and DBP) was analyzed for association with genotypes at the ACE gene locus. The DD genotype was observed in 132 patients (25.5%), the ID genotype in 255 patients (49.3%), and the II genotype in 130 patients (25.2%). The SBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -14.5 +/- 12.7 mmHg, -14.3 +/- 13.1 mmHg and -14.0 +/- 12.2 mmHg, respectively (p = 0.94). The DBP reductions in the patients with the DD genotype, II genotype, and ID genotype were -8.7 +/- 7.4 mmHg, -8.7 +/- 7.7 mmHg and -8.5 +/- 6.7 mmHg, respectively (p = 0.96). There was no significant association between the ACE gene polymorphisms and the response to ACE inhibition. These results suggest that ACE genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibition.     

I/D gene polymorphism of the angiotensin-converting enzyme and left ventricular hypertrophy. Response to converting enzyme inhibitors

BACKGROUND: The present study was designed to assess whether the angiotensin-converting enzyme (ACE) gene I/D polymorphism influence the ACE inhibitors effect on the regression of left ventricular hypertrophy. METHODS: Sixty hypertensive subjects never treated by antihypertensive drugs, aged 46 +/- 11 years, were included in the study. Follow-up with ACE inhibitor treatment was 60 +/- 26 months. Genotypes for ACE I/D polymorphism (DD, ID or II) were determined by PCR. The left ventricular mass index (LVMI) was assessed by two-dimensional directed M-mode echocardiography. RESULTS: ACE genotype distribution was in agreement with the Hardy-Weinberg equilibrium: 21 patients had the DD genotype, 29 were ID, and 10 were II. At baseline, age, systolic arterial pressure and LVMI didn't differ on the basis of genotype. Body mass index was significantly higher in II than in ID and DD groups. Regression of LVMI with ACE inhibitor treatment was similar in the 3 genotypes (-8.9%, -0.6%, -12.1% in DD, ID and II groups respectively). In addition, decrease of systolic arterial pressure was identical in 3 groups. CONCLUSION: ACE gene I/D polymorphism seems not to influence regression of left ventricular hypertrophy by ACE inhibitors in essential hypertension.     

Atherosclerosis of carotid arteries and the ace insertion/deletion polymorphism in subjects with diabetes mellitus type 2.

BACKGROUND: The aim of the present study was to investigate the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the ultrasonographically evaluated severity and characteristics of carotid artery atherosclerosis in subjects with diabetes mellitus type 2. METHODS: We assessed 184 subjects with diabetes mellitus type 2, 75 males and 109 females, mean age 61.4+/-7.7 years. All subjects were receiving oral antidiabetic drugs for glycemic control and were free of cardiovascular events. The ACE genotype was analyzed by the polymerase chain reaction (PCR) technique. The ultrasonographic examination of the carotid arteries was performed in both B-mode imaging and Doppler ultrasound. The common carotid artery intima-media thickness was assessed 15-20 mm proximal to the dilatation of the carotid bulb. The atheromatous lesions were classified according to their echogenic characteristics as predominantly echolucent, mixed and predominantly echogenic with under 30, 30-70 and over 70% of the total plaque area echogenicity, respectively. RESULTS: From the total cohort 29 (15.8%) subjects had the II, 86 (46.7%) the ID and 69 (37.5%) the DD ACE genotypes. The mean carotid artery diameter stenosis was 37+/-17%, 43+/-19% and 40+/-20% (p=NS) and the intima media thickness was 0.94+/-0.24 mm, 0.97+/-0.20 mm and 0.98+/-0.20 mm (p=NS) in the II, ID and DD subgroups, respectively. When the echogenicity was analyzed according to the ACE I/D polymorphism, 12 subjects (41.4%), 13 (44.8%) and 4 (13.8%) with II genotype had predominantly echogenic, mixed and predominantly echolucent lesions, respectively. The ID genotype diabetics were found to have predominantly echogenic plaques in 41 cases (47.7%), mixed in 30 (34.9%) and predominantly echolucent in 15 cases (17.4%). From the 69 DD subjects 19 (27.5%) had predominantly echogenic plaques, 26 (37.7%) had mixed and 24 (34.8%) had predominantly echolucent lesions. Predominantly echolucent plaques were more frequently encountered among diabetics with the DD genotype (p<0.05), even after correction for demographic characteristics, the main risk factors of atherosclerosis and blood glucose control. CONCLUSIONS: The ACE genotype seems to be associated with the echogenicity of carotid artery atheromatosis but not with the common carotid artery intima media thickness or the degree of internal carotid artery stenosis in subjects with type 2 diabetes mellitus. The DD genotype may be implicated in the increased cardiovascular risk that characterizes echolucent plaques.     

Angiotensin-II type 1 receptor gene polymorphism and long-term survival in patients with idiopathic congestive heart failure

BACKGROUND: It has been suggested that a genetic polymorphism in the angiotensin II type 1 receptor gene (ATRG) and the ACE gene DD genotype might have a synergistic influence on the risk of developing cardiovascular disease. Aims: To study the possible interaction between polymorphisms in the ACE gene and the ATRG, regarding survival and left ventricular function. METHODS: Polymorphism of the two genes was studied in a population-based cohort of 194 patients with idiopathic heart failure, recruited from the western part of Sweden 1985-1988. The patients were investigated by echocardiography. The survival status was checked during the 7-year follow-up period. RESULTS: Although there was no statistically significant additive risk of the ATRG polymorphism, patients carrying the ACE gene DD genotype in combination with a C allele of the ATRG tended to have a poorer prognosis. DD +AA, OR 1.24 (95% CI 0.67-2.32, P = 0.49); DD +AC, OR 1.64 (95% CI 0.95-2.83, P = 0.08); DD + CC, OR 3.54 95% CI 0.78-16.1, P = 0.10); DD +AC/CC, OR 1.84 (95% CI 1.10-3.08, P = 0.02). Patients with the DD +AC/CC genotypes tended to have lower ejection fraction and increased left ventricular mass. CONCLUSIONS: There was a trend toward a worse prognosis in patients with the combination of a C-allele in the ATRG and the ACE gene DD genotype, suggesting an interaction of these two genetic polymorphisms on disease severity.     

Effects of angiotensin-converting enzyme polymorphism on aortic elastic parameters in athletes

BACKGROUND: Physiologic adaptations in an athlete's heart include increased left and right ventricular chamber size, left ventricular wall thickness and mass. Angiotensin-converting enzyme (ACE) is a key enzyme in angiotensin II production causing cardiac hypertrophy. The cloning of the ACE gene has made it possible to identify a deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. Therefore, the ACE genes, which have been shown to be polymorphic, could be candidate genes for large-artery stiffness. METHODS: 56 endurance athletes and 46 sedentary subjects were included in this study, and they underwent both complete echocardiographic examination, and analysis of ACE insertion (I) and deletion (D) allele frequencies in peripheral blood. The aortic diameter was recorded by M-mode echocardiography at a level 3 cm above the aortic valve. Aortic systolic diameter was measured at the time of full opening of the aortic valve, and diastolic diameter was measured at the peak of QRS. Aortic strain, stiffness index and distensibility were calculated. RESULTS: Left ventricular mass index and left ventricular ejection fraction were significantly higher in athletes than controls (p < 0.001). The aortic distensibility index and strain were significantly greater in athletes compared with controls (respectively: 5.8 +/- 2.7 vs. 4.7 +/- 1.8 cm(-2) dyn(-1) 10(-6), p = 0.017; 12.3 +/- 2.4 vs. 9.3 +/- 3.1, p < 0.001). The aortic stiffness index was significantly lower in athletes than in controls (4.8 +/- 1.9 vs. 6.1 +/- 2.1, p < 0.001). The aortic distensibility index and strain were statistically different in ACE DD vs. DI groups and DD vs. II groups of athletes. The aortic stiffness index was statistically different in ACE DD vs. II groups of athletes. Aortic parameters were similar according to ACE genotypes in controls. CONCLUSION: The results of this study indicate that aortic distensibility was increased by prolonged training in endurance athletes, particularly in those with the ACE II genotype. This effect represents an extracardiac adaptation to chronic prolonged training in athletes.     

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。     

Angiotensin-converting enzyme gene I/D polymorphism increases the susceptibility to hypertension and additive diseases: A study on North Indian patients

Angiotensin-converting enzyme (ACE) is the key enzyme of the renin angiotensin system (RAS) which maintains the blood pressure homeostasis in our body. The association of the ACE insertion/deletion (I/D) polymorphism with essential hypertension has been demonstrated by many studies. The purpose of the present study is to investigate the association of the insertion/deletion polymorphism of the ACE gene with hypertension and additive diseases in North Indian population. In total, 222 hypertensive and 218 normotensive adults participated in this hospital-based study. Anthropometric measures, lipids profiles, blood glucose, and blood pressure (BP) measures were collected from participants. ACE I/D polymorphism was determined by using insertion-specific amplification. The mean ages of study groups were 50.35 ± 12.40 and 47.32 ± 11.94 for cases and controls, respectively. Significant differences were observed in the frequencies of DD, ID, and II genotypes among the hypertensive and normotensive groups which were found to be 29.7%, 38.7%, and 31.5% vs. 53.7%, 23.4%, and 22.9%, respectively. It has been observed that the ACE ID genotype was significantly (p < 0.05) higher in hypertensive subjects, whereas, the DD genotype was significantly (p < 0.05) higher in control subjects. A strong association was found between cardiovascular diseases (CVDs) and ID genotype [p = 0.017, odds ratio (OR) = 3.091, 95% confidence interval (CI) = 1.224–7.807]. ID [p = 0.002, OR = 2.020, 95% CI = 1.281–3.185] and II [p = 0.032, OR = 1.677, 95% CI = 1.044–2.694] genotypes are more prone to diabetes with hypertension. This finding suggests that ACE insertion/deletion polymorphism is associated with hypertension and additive diseases in North Indians.     

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.     

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects

Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and hypertension. Recent studies of population-based samples of three different areas in Japan presented conflicting results regarding this association. We, thus, investigated the relation between the ACE I/D polymorphism and blood pressure (BP), or the frequency of hypertension, respectively, in 706 Japanese male subjects who participated in the health check-up programme of our hospital. The ACE I/D polymorphism was determined by the polymerase chain reaction technique. Of 706 subjects, 203 were found to have hypertension and the other 503 were found to be normotensive. In all subjects, the frequencies of the DD, ID, and II genotypes were 0.123, 0.432, and 0.445, respectively, and the allelic frequency of the D allele was 0.339. In the younger subjects aged <50 years (n=264), neither systolic nor diastolic BP differed significantly among the genotypes. Conversely, in the older subjects aged > or =50 years (n=442), the systolic BP was significantly higher by 5.9 mmHg in the subjects with the ID genotype than those with the II genotype (P<0.01), and the diastolic BP was significantly higher in the subjects with the DD and ID genotypes by 5.1 and 3.3 mmHg, respectively than those with the II genotype (P<0.05 for each), although age, BMI, percentage of smoking habits, drinking habits, or the use of antihypertensive drugs did not differ significantly among the genotypes. In addition, in the older subjects, the hypertensive subjects showed significantly higher frequencies of the DD and ID genotypes and the D allele than the normotensive subjects. These results demonstrated that there was no significant association of the ACE I/D polymorphism with BP or a prevalence of hypertension in younger Japanese men aged <50 years but there was in older Japanese men aged > or =50 years.