Angiotensin-converting enzyme gene polymorphism in coronary artery disease in north India

BACKGROUND: The aim of this study was to investigate the role of angiotensin-converting enzyme gene polymorphism in patients with coronary artery disease in north India. METHODS AND RESULTS: One hundred forty-six patients with angiographically proven atherosclerotic coronary artery disease, and 146 age- and sex-matched control subjects (treadmill-negative) were included in the study. Genomic DNA was extracted and analyzed for angiotensin-converting enzyme insertion/deletion polymorphism. Two independent investigators scored the genotypes. CONCLUSIONS: When we compared the genotypes of patients with coronary artery disease with those of normal controls, it was seen that all three genotypes, i.e. DD, ID and II, were not statistically different among patients and controls. Further, we categorized the patient and control groups into 2 subgroups, i.e. below and above 50 years of age. Interestingly, it was observed that the DD genotype was significantly higher in patients in the higher age group (i.e. above 50 years of age). However, this needs further validation by studying patients with coronary artery disease from other parts of India.     

Angiotensin-converting enzyme gene polymorphism in patients with psoriatic arthritis

To investigate the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in adults with psoriatic arthritis (PsA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanism. The frequency of ACE gene I/D polymorphism genotypes was determined in 51 adults with PsA from Kuwait, and compared to that in 100 ethnically matched healthy controls using polymerase chain reaction. The distribution of ACE I/D polymorphism and allele frequencies in PsA patients were not significantly different from controls (P > 0.05). Further analyses of PsA patients showed that ACE I/D gene polymorphism was not associated with family history, clinical manifestations, and disease severity. However, the frequency of II genotype was significantly higher in patients with late disease onset than in those with early onset (25 vs. 3%; P = 0.04). No difference was found between the distribution of the ACE genotype in PsA patients and the general population in Kuwait. However, the presence of II genotype may confer susceptibility to the development of late onset PsA.     

Angiotensin-converting enzyme gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients

OBJECTIVE: It has been suggested that the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) may be associated with atherosclerosis.The aim of the study was to examine the association between ACE gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients. METHODS AND RESULTS: A total of 152 (97 female, 55 male) type 2 diabetic patients were included into the study. All patients underwent myocardial perfusion scintigraphic examination and forty-five of them with a perfusion defect underwent coronary angiography.Thirty-eight patients with a coronary stenosis of more than 50% on coronary angiography were considered as having coronary heart disease.The I/D polymorphism was determined by polymerase chain reaction.There was no statistically significant difference in genotypic and allelic frequencies of the ACE I/D polymorphism among patients with and without coronary heart disease (DD:ID:II (%), 32:58:11 and 39:44:17, respectively). CONCLUSIONS: ACE gene polymorphism is not a significant parameter to determine coronary heart disease in Turkish type 2 diabetic patients.     

血管紧张素转换酶基因多态性与卒中

血管紧张素转换酶(angiotensin converting enzyme,ACE)基因是卒中遗传易感性研究的主要候选基因之一,但ACE基因多态性与卒中的相关性还存在着争议.文章就近年来有关ACE基因多态性与卒中相关性的研究进展进行了综述.     

Angiotensin-converting enzyme gene polymorphism in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is often accompanied by cardiovascular and metabolic disorders. The renin-angiotensin system plays an important role of the cardiovascular regulation. The activity of the angiotensin converting enzyme is genetically determined. The aim of the study was to estimate the relation between angiotensin converting gene polymorphism and cardiovascular diseases or familial history in patients with obstructive sleep apnea. 63 patients with OSA were enrolled to the study. Arterial hypertension was diagnosed in 30 cases, ischaemic heart disease in 5 cases and 10 patients suffered from both mentioned diseases. RESULT: The observed ACE genotype frequencies in the study group were II: ID: DD: 23.81: 47.62: 28.57%, in the hypertension subgroup II: ID: DD--30.0: 46.6: 23.3%. No differences in the study group were observed in relation to familial history :DI:II--30.43: 43.48: 26.09% vs 25.64: 48.72: 25.4%. CONCLUSIONS: 1. In the study group there was no association between ACE polymorphism and OSA. 2. There were also no association between the polymorphism of ACE and cardiac diseases or familial history of cardiac diseases in OSA group. 3. The polymorphism of ACE is not a risk factor for OSA.     

Angiotensin-converting enzyme gene polymorphism in Kuwaiti patients with systemic lupus erythematosus

OBJECTIVE: To investigate the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in patients with systemic lupus erythematosus (SLE), and to study the correlation between I/D polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement, lupus nephritis and disease severity. METHODS: The frequency of ACE gene I/D polymorphism genotypes was determined in 92 patients with SLE from Kuwait, and compared to that in 100 ethnically matched healthy controls using the polymerase chain reaction. RESULTS: The distribution of ACE I/D polymorphism and allele frequencies in SLE patients was not significantly different from controls. Further analyses of SLE patients showed that there was a significant association between DD genotype and Raynaud's phenomenon (p=0.008, odd ratio=5.4, 95% confidence interval: 1.6-18.6). However, there was no significant association between the ACE genotype and lupus nephritis or disease severity. CONCLUSION: No difference was found between the distribution of the ACE genotype in SLE patients and the general pop-ulation in Kuwait. However, the presence of the DD genotype may confer susceptibility to the development of vascular morbidity.     

Angiotensin-converting enzyme gene polymorphism in patients with primary disturbances of cardiac conduction

Increased frequencies of angiotensin-converting enzyme (ACE) D-allele and ID-genotype among patients with idiopathic atrioventricular blocks and I allele and II genotype among patients with idiopathic intraventricular blocks allow to consider these genotypes risk factors of corresponding disturbances of cardiac conduction. Decreased frequency of ACE I allele and II genotype among patients with idiopathic atrioventricular blocks is indicative of a possible protective role of II genotype against development of this type of cardiac conduction defect. Low frequency of D allele and genotype D prevents derangements of conduction in His-Purkinje system.     

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 and apolipoproteins genes polymorphism in coronary artery disease

BACKGROUND: Association between angiotensin-converting enzyme (ACE) as well as apolipoprotein (apo) AI, B, and E polymorphisms and dyslipidemia and coronary artery disease (CAD) is controversial. HYPOTHESIS: This study assessed the distribution of ACE insertion/deletion, apo AI A/G mutation, apo B signal peptide insertion/deletion, apo B XbaI restriction fragment length, and apo E polymorphisms in 388 nondiabetic patients. METHODS: The study population included 112 patients with stable CAD, 139 patients with acute myocardial infarction (AMI), and 137 age-matched control subjects. RESULTS: Univariate analysis showed higher prevalence of XbaI X+/X+ genotype in patients with CAD (p = 0.02). Angiotensin-converting enzyme and apo polymorphisms were not associated with lipid levels or severity of CAD. When all genotypes known to be related to CAD; such as ACE DD, apo AI GG, apo B del/del, and XbaI X+X+, and E4 allele of apo E, were pooled, again no significant differences among groups were seen. Multivariate regression analysis disclosed traditional risk factors and elevated levels of apo B for men and reduced levels of apo AI for women as independent variables for CAD. CONCLUSIONS: In addition to traditional coronary risk factors, apo B and AI could be considered predictors of CAD. No association between either form of CAD and polymorphisms was noted.     

Angiotensin-converting enzyme and angiotensinogen gene polymorphism in hypertrophic cardiomyopathy

To examine the contribution of the renin-angiotensin system to hypertrophic cardiomyopathy (HCM), the authors studied 96 patients with HCM (mean age 50 years, 55% male), 105 of their unaffected siblings and offspring, and 160 healthy subjects without known hypertension and left ventricular hypertrophy who were frequency matched by age and sex. Patients were divided into familial or sporadic HCM (FHCM or SHCM) groups with or without affected family members. The T allele frequency was higher in the SHCM group than in unaffected siblings and offspring (88% versus 78%, χ²=4.6, P<0.05). The M allele frequency was higher in unaffected siblings and offspring than in patients with SHCM (23% versus 12%, χ²=4.6, P<0.05). The T allele frequency among unaffected siblings and offspring was similar to that observed in healthy subjects (78% versus 78%). The molecular variant of angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy in HCM and carries an approximately twofold increased risk. The authors also determined angiotensin-converting enzyme gene insertion/deletion polymorphism. The D allele frequency was higher in SHCM than in FHCM. The findings suggest that HCM, especially in solitary cases, is partially determined by genetic disposition. These results also suggest that angiotensin-converting enzyme and angiotensinogen gene polymorphism are genetic contributing factors associated with cardiac hypertrophy in HCM.     

Angiotensin-converting enzyme gene polymorphism and microvascular complications in Turkish type 2 diabetic patients

The aim of this study was to investigate whether an association exists between the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and microvascular complications of type 2 diabetes mellitus in Turkish patients. A total of 239 type 2 diabetic patients and 138 sex and age matched control subjects were included into the study. The I/D polymorphism was determined by polymerase chain reaction (PCR). Nephropathy status was determined according to urinary albumin/creatinine ratio (microg/mg) (<30 normoalbuminuria, 30-300 microalbuminuria, >300 macroalbuminuria) and retinopathy was evaluated by fundoscopic examination and by flourescein fundus angiography. The distribution of ACE I/D polymorphism and allele frequencies in diabetic patients were not significantly different from controls, DD genotype 32.2 versus 37.2%; ID genotype 50.6 versus 47.1%; and II 17.2 versus 15.2%; D allele 57.5 versus 61.2%; I allele 42.5 versus 38.8%. Genotype distribution between normo-, micro- and macroalbuminuric patients did not differ significantly (DD:ID:II (%), normoalbuminuria, 35:46:19; microalbuminuria, 28:55:17; macroalbuminuria, 31:55:14). There was also no difference in genotype distribution between patients with and without retinopathy (DD:ID:II (%), retinopathy positive, 32:51:17; retinopathy negative, 33:49:18). In conclusion, the ACE I/D polymorphism does not seem to be associated with diabetic nephropathy and retinopathy in Turkish type 2 diabetic patients.     

Angiotensin-converting enzyme gene polymorphism in relation to HLA-DR in sarcoidosis

OBJECTIVES: To investigate if an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene associates with HLA-DR alleles previously found to be of prognostic interest in Scandinavian sarcoidosis patients. This may contribute to characteristics associated with these HLA-DR alleles, such as a good (DR17) or poor (DR14 or 15) prognosis. DESIGN, SETTINGS AND SUBJECTS: Polymerase chain reaction (PCR) was used for analysing an I/D polymorphism in the gene coding for ACE in 138 subjects; 65 controls and 73 sarcoidosis patients, and for HLA-DR genotyping 67 patients. Serum ACE level (S-ACE) was measured in all controls and 72 patients. Sixty-one patients were classified as chronic or nonchronic after 2 years follow-up. All patients were recruited and followed at our outpatient clinic. RESULTS: No significant differences in ACE alleles or genotypes were seen between controls and patients or between patients positive and negative for DR17 or DR14/15. The ACE genotype did not differ between nonchronic and chronic patients. The ACE genotype tended to influence the S-ACE in patients, whilst in controls S-ACE significantly differed between the ACE genotypes. CONCLUSION: This study does not support an association between ACE genotype and sarcoidosis or disease outcome. However, because significantly (P < 0.001) more DR17 positive (17 of 19) than DR14/15 positive (seven of 26) patients were classified as nonchronic, these results instead strengthen the prognostic importance of HLA-DR alleles in Scandinavian sarcoidosis patients.     

Angiotensin-converting enzyme gene I/D polymorphism in malignant hypertension

BACKGROUND: The mechanism of the rapid transition of a stable benign hypertensive disease to a severe and devastating malignant hypertension is not fully understood. However, the renin angiotensin system, which is highly activated in malignant hypertension, is established as an important pathogenetic factor in different cardiovascular and renal diseases. Over the last decade, a polymorphism in genes regulating this system has been found. This includes the 287 bp sequence deletion (D)/insertion (I) polymorphism in the angiotensin-converting enzyme (ACE) gene and the methionine (M) to threonine (T) point mutation polymorphism in the angiotensinogen (AGT) gene. These gene polymorphisms have been associated with various cardiovascular and renal diseases and the aim of this study was to investigate whether they were linked to malignant hypertension. METHODS: Forty-two patients with malignant hypertension (mean age 55 years), 42 patients with non-malignant hypertension (mean age 57 years) and 85 normotensive control subjects (mean age 42 years) were investigated with respect to ACE I/D and AGT M/T genotypes. DNA was prepared by standard methods from isolated white blood cells and analysed by the PCR technique. The PCR reaction used in the detection of the ACE I/D polymorphism was optimized for an equal amplification of the I and D alleles. RESULTS: The frequency of the DD genotype was significantly increased in patients with malignant hypertension (43%) compared with patients with non-malignant hypertension (14%) and normotensive control subjects (18%) (p <0.01) for both. The frequency distribution of AGT M/T genotype did not differ between patients with malignant and non-malignant hypertension. CONCLUSION: The DD genotype of the ACE gene occurred more than twice as often in malignant hypertension than in non-malignant hypertension and indicates that ACE gene polymorphism is a significant risk factor for initiation of malignant hypertension.     

Angiotensin-converting enzyme inhibitors in patients with coronary atherosclerosis

Activation of the renin-angiotensin-aldosterone system has been shown to be an independent risk factor for myocardial infarction (MI). The importance of this risk factor has been confirmed by the finding that patients with a DD genotype for the angiotensin-converting enzyme (ACE) gene, which is associated with increased serum ACE levels, have a higher incidence of MI than do patients without this genotype. ACE inhibitors have been shown to significantly reduce the incidence of recurrent MI in patients with left ventricular dysfunction. The mechanism by which activation of the renin-angiotensin-aldosterone system leads to MI has not been ascertained, but it may be related to the effect of angiotensin II or aldosterone on the development of atherosclerosis, endothelial dysfunction, plaque rupture, or thrombosis after plaque rupture. Experimental data suggest that each of these mechanisms may be of importance. Several prospective randomized studies are under way to determine the effect of ACE inhibitors on recurrent ischemic events and the progression of atherosclerosis in patients without left ventricular dysfunction. If these studies yield positive results, ACE inhibitors might assume an important role in the secondary and possibly primary prevention of ischemic heart disease.     

Angiotensin-converting enzyme gene polymorphism is correlated to diabetic retinopathy: a meta-analysis

The angiotensin-converting enzyme (ACE) displays potent vasoconstrictive effects, attenuation of fibrinolysis, and platelet activation and aggregation. The ACE gene has been the main probable candidate gene predisposing the development of diabetic retinopathy (DR). However, the correlation between ACE gene polymorphism and progression of DR still requires further approval. Here, the author performs a summative analysis on recent previous reports on ACE gene polymorphism and its correlation to DR. The meta-analysis was performed in order to assess the correlation between the pattern of ACE gene polymorphism and DR. From four studies available, the author evaluated type II diabetic patients with (Group 1; n=432) and without DR (Group 2; n=329). The frequency of the DD genotype in Group 1 is not significantly different from that in Group 2 (P>.05). In addition, the author first reports a nonsignificant correlation between ethnicity and ACE gene polymorphism.     

Angiotensin-converting enzyme gene polymorphism and carotid wall thickening in a community population.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of coronary heart disease, but whether it is a risk factor for underlying atherosclerosis remains unclear. Therefore, we examined to see whether the ACE gene deletion polymorphism was associated with carotid wall thickening and atherosclerotic plaque formation in a large randomly selected community population. A total of 1111 subjects, aged 27 to 77 years, with an equal male:female ratio and equal numbers in each age decile, were randomly selected from the Perth community population. Mean common carotid intima-medial wall thickness (IMT) and focal plaque formation were assessed by high-resolution B-mode ultrasound. The ACE gene I/D polymorphism was detected by PCR. The distribution of the ACE genotypes conformed to the Hardy-Weinberg equilibrium (DD, 31.0%; ID, 48.4%; and II, 20.6%). The D allele was strongly correlated in a codominant fashion with plasma ACE activity (r(s)=0.53, P<0.0001), and accounted for 33% of the total variance in circulating ACE activity. No significant differences among the ACE genotypes were found with respect to age, sex, and conventional risk variables, including a history of hypertension and vascular disease. The average mean IMT and prevalence of increased IMT and focal plaque were not significantly different among genotypes in the overall population or in the subset (n=852) who were conventionally low risk by Framingham coronary heart disease risk score. Logistic regression analysis selected age, systolic blood pressure, pack-years of smoking, LDL cholesterol level, waist/hip ratio, and history of hypertension, but not the D allele, as multivariate predictors of increased IMT and carotid plaque formation. We conclude that, although the ACE I/D polymorphism is strongly related to ACE activity, it is not a risk predictor of carotid wall thickening or focal plaque formation when examined in a large randomly selected community population.     

Angiotensin-converting enzyme insertion/deletion gene polymorphism in inflammatory bowel diseases

INTRODUCTION: The renin-angiotensin system is strictly related to the kallikrein-kinin system and both are involved in many physiological and disease conditions and possibly in the pathogenesis of inflammatory bowel disease (IBD). Angiotensin-converting enzyme (ACE) is the pivotal enzyme of the renin-angiotensin system and the main catabolic enzyme of the kallikrein-kinin system. The ACE I/D (insertion/deletion) is a polymorphism of the gene encoding for ACE: participants who are homozygous for the D allele exhibit higher ACE levels, which in turn appear to play a deleterious role in several diseases. AIM: To study the prevalence of ACE I/D polymorphism in IBD patients and its possible association with disease features. METHODS: A total of 232 IBD patients, 124 with ulcerative colitis (UC) and 108 with Crohn's disease and 99 healthy controls were genotyped for the ACE I/D polymorphism. RESULTS: DD, ID and II genotypes distribution did not show significant differences between IBD patients and controls: 42.2 vs. 40.4%, 42.7 vs. 47.5% and 15.1 vs. 12.1%, respectively. No significant difference was observed between Crohn's disease and UC patients. Within UC patients, the presence of DD genotype and the carriage of the D allele were significantly associated with the presence of extraintestinal manifestations: odds ratio (OR) 4.08, 95% confidence interval (CI): 1.62-10.28; P<0.003 and OR=3.07, 95% CI: 1.45-6.48; P<0.003, respectively. No significant association was found with other IBD clinical features. CONCLUSIONS: The ACE I/D polymorphism is not associated with IBDs but the D allele appears to increase the risk of developing extraintestinal manifestations in UC patients.     

Angiotensin-converting enzyme i/d polymorphism in patients with malignant hypertension

The angiotensin-converting enzyme (ACE) gene has been implicated in the manifestation of the phenotype of malignant hypertension (MH). In 1990 the ACE gene polymorphism characterized by the insertion or deletion of a 287-base pair fragment in the 17q23 chromosome was identified. The DD genotype is associated with increased tissue and circulating ACE levels and elevated angiotensin II. ACE polymorphism was studied in 48 patients with MH, 25 patients with non-MH, and a control group of 78 normotensive individuals by real-time polymerase chain reaction using the LightCycler system (Roche Diagnostics Corporation, Indianapolis, IN). The DD genotype was found statistically more frequently in MH patients than controls (p=0.028; odds ratio, 2.5; confidence interval, 1.1-5.5). Presence of the DD genotype of the ACE gene is more frequent in MH patients than in controls, indicating that this genotype could be a significant risk factor and a predictor for the development of MH.