The association of ACE gene D/I polymorphism with cardiovascular risk factors in a population from Rio de Janeiro

Our aim was to determine the frequencies of the angiotensin-converting enzyme (ACE) gene alleles D and I and any associations to cardiovascular risk factors in a population sample from Rio de Janeiro, Brazil. Eighty-four adults were selected consecutively during a 6-month period from a cohort subgroup of a previous large cross-sectional survey in Rio de Janeiro. Anthropometric data and blood pressure measurements, echocardiogram, albuminuria, glycemia, lipid profile, and ACE genotype and serum enzyme activity were determined. The frequency of the ACE*D and I alleles in the population under study, determined by PCR, was 0.59 and 0.41, respectively, and the frequencies of the DD, DI, and II genotypes were 0.33, 0.51, and 0.16, respectively. No association between hypertension and genotype was detected using the Kruskal-Wallis method. Mean plasma ACE activity (U/mL) in the DD (N = 28), DI (N = 45) and II (N = 13) groups was 43 (in males) and 52 (in females), 37 and 39, and 22 and 27, respectively; mean microalbuminuria (mg/dL) was 1.41 and 1.6, 0.85 and 0.9, and 0.6 and 0.63, respectively; mean HDL cholesterol (mg/dL) was 40 and 43, 37 and 45, and 41 and 49, respectively, and mean glucose (mg/dL) was 93 and 108, 107 and 98, and 85 and 124, respectively. A high level of ACE activity and albuminuria, and a low level of HDL cholesterol and glucose, were found to be associated with the DD genotype. Finally, the II genotype was found to be associated with variables related to glucose intolerance.

The Effect of ACE Gene Polymophism on the Antiproteinuric Effect of Angiotensin II Receptor Antagonist in Patients with Non-diabetic Chronic Renal Disease / 대한신장학회잡지

BACKGROUND: Angiotensin II, a potent vasoconstrictor, plays a key role in renal injury and in the progression of chronic renal disease of diverse causes. In every organ system, the biologic effects of angiotensin II are mediated through its interaction with specific receptors on cell membranes. Angiotensin II receptor antagonist specifically inhibits angiotensin II-mediated physiologic responses such as systemic and renal vasoconstriction, sodium reabsorption by renal proximal tubule, and stimulation of aldosterone and adrenergic hormone release by the adrenal gland. It has been reported that losartan, angiotensin II receptor antagonist, has a significant antiproteinuric effect in patients with diabetic and non-diabetic renal disease. This study was carried out to investigate the effect of angiotensin-converting enzyme (ACE) gene polymorphism on the renal response to angiotensin II receptor antagonist in non-diabetic proteinuric chronic renal patients. METHODS: Seventy patients with non-diabetic chronic renal disease with urinary protein excretion greater than 500 mg/day were enrolled in this prospective study. Subjects were given losartan 50 mg o.d. for the first 12 weeks, and then were given to 100 mg o.d. for another 12 weeks. RESULTS: Twelve weeks and twenty-four weeks later, blood pressure, urinary protein excretion, total cholesterol, and triglyceride decreased significantly compared with baseline values. There was a significant correlation between the levels of baseline urinary protein excretion and the magnitudes of the reduction of urinary protein excretion after treatment with losartan. Baseline blood pressure, BUN, serum creatinine, and urinary protein excretion were not different in the responder group (patients with more than 30% reduction of urinary protein excretion after losartan treatment) compared with the nonresponder group. Systolic blood pressure and mean arterial pressure in the responder group were significantly lower than the nonresponder group after twelve and twenty-four weeks. Urinary protein excretion in the responder group was significantly lower than the nonresponder group after twelve weeks. When the patients were divided into three groups according to ACE gene polymorphism, II, ID and DD, there were no significant differences in the blood pressure change, reduction of urinary protein excretion following losartan treatment and distributions of responder among three groups. CONCLUSION: Our results suggest that angiotensin II receptor antagonist, losartan, significantly reduced blood pressure and proteinuria in patients with non- diabetic chronic renal disease. The magnitude of antiproteinuric effect of losartan was not influenced by ACE gene polymorphism. However, further studies with large number of patients are required to confirm the issues regarding the ACE gene polymorphism and the antiproteinuric effects of angiotensin II receptor antagonist in non-diabetic chronic renal disease.

Role of ACE Gene Polymorphism on the Failure of Arteriovenous Fistulae for Maintenance Hemodialysis / 대한신장학회잡지

BACKGROUND: Neointimal hyperplasia and thrombosis are the major factors responsible for vascular access occlusion. Previous studies suggested that the renin-angiotensin system has been implicated in the pathogenesis of neointimal hyperplasia and thrombosis. Recent studies have shown that angiotensin-converting enzyme (ACE) gene polymorphism may have a association with venous thrombosis. We conducted a retrospective case control study to determine the influence of ACE gene polymorphism on the progression of radiocephalic wrist arteriovenous fistulae (RCAVF). Also, we investigated the association between ACE polymorphism and various thrombotic factors in thrombosed and nonthrombosed subjects. METHODS: 56 patients (24 males and 32 females, mean age 49.8, age range 12-81) whose RCAVF had been maintained in good condition after 2 months of vascular access operation were included in this study. Lipoprotein (a), total cholesterol, C-reactive protein (CRP) and homocystein were measured before hemodialysis session in fasting state. Clinical data such as body mass index (BMI), cigarette smoking, hypertension, and diabetes were retrieved from patient's records. The ACE genotype was analyzed by the polymerase chain reaction (PCR). RESULTS: The incidence of diabetes and cigarette smoking were similar in the three genotypes. There were no significant differences in BMI, total cholesterol, lipoprotein (a), CRP and homocystein (p=0.551, 0.429, 0.279, 0.392, 0.124, respectively) among DD, ID and II genotypes. The percentage of the DD, ID and II genotypes were 16%, 43%, 41%, respectively. Compared with the ID and II genotypes, the proportion of the thrombosed AV shunts was larger in DD genotypes. But there was no statistically significant difference between ACE polymorphism and RCAVF thrombosis (x2=1.027, df=2, p=0.598). ACE polymorphism is shown to have no association with body mass index, blood level of total cholesterol, lipoprotein (a), CRP and homocystein. CONCLUSION: These results suggest that ACE polymorphism may have some influences on the vascular access occlusion in maintenance hemodialysis patients and have no relationship with body mass index, total cholesterol, lipoprotein (a), CRP and homocystein.

Polymorphisms of Angiotensin Converting Enzyme and Plasminogen Activator Inhibitor-1 Genes in Diabetic Nephropathy and Macroangiopathy in NIDDM Patients / 대한신장학회잡지

BACKGROUND: Although development of DM nephropathy in NIDDM patients is associated with poorly controlled blood sugar level and hypertension, relationship of genetic factor is also emphasized. Recent studies showed that an insertion or deletion (I/D) polymorphism in the ACE gene and a 4/5- guanine tract polymorphism in the promotor region of the PAI-1 gene are associated with the myocardial infarction. The aim of this study were to determine the relationships of these polymorphism and substance activities to DM nephropathy and macroangiopathy. METHODS: 72 NIDDM patients who suffered from DM more than 6 years and 62 non-diabetic healthy control were evaluated. After extraction of DNA from peripheral blood, ACE and PAI-1 gene polymorphisms were determined by polymerase chain reac tion, SSCP electrophoresis and silver stain. Serum PAI-1 level was dctected by Immulyse PAI-1 ELISA kit(Bipool Sweden). RESULTS: Total 134 samples were evaluated and ACE genotype were DD 27(20%), ID 88(66%), and II 19(14%). PAI-1 genotype were 4G4G 26(19%), 4G5G 73(55%), and 5G5G 35(26%). The distribution of ACE and PAI-1 polymorphism according to presence or absence of nephropathy were DD 10, ID 32, II 8, 4G4G 9, 4G5G 31, and 5G5G 10 in DM nephropathy group and DD 3, ID 17, II 2, 4G4G 5, 4G5G 12, and 5G5G 5 in non-nephropathy group. There were no significant differences in the distribution of ACE and PAI-1 gene between the two groups. The distribution of ACE and PAI-1 polymorphism according to macroangiopathy were DD 6, ID 16, II 3, 4G4G 5, 4G5G 15, and 5G5G 5 in macroangiopathy group and DD 7, ID 33, II 7, 4G4G 9, 4G5G 28, and 5G5G 10 in non-macroangiopathy group. There were no significant differences in the distribution of ACE and PAI- 1 gene between macroangiopathy and non-macroangiopathy groups. Serum PAI-1 level according to PAI-1 gene and ACE gene polymorphism were 4G4G 47.99+/-19.73, 4G5G 40.19+/-18.49, 5G5G 40.37+/-20.99 ng/mL, DD 37.99+/-16.64, ID 44.80+/-20.35, and II 31.92+/-12.98 and had a tendency that is higher in 4G4G genotype. CONCLUSION: From the above results, we cannot define the relationships of ACE and PAI-1 gene polymorphism and PAI-1 activities to DM nephropathy and macrovascular complications of NIDDM patients, but prospective studies including more patients population will be required.

Association between the insertion/deletion polymorphism of angiotensin converting enzyme gene and the myocardial infarction / 中国综合临床

Objective To investigate the association between the insertion/deletion(I/D) polymorphism of angiotensin converting enzyme (ACE) gene and the myocardial infarction (MI) among Chinese population. Methods Polymerase chain reaction(PCR) was applied to the examination of ACE gene polymorphism. A comparison was performed between 50 patients with MI and another 50 healthy subjects.Results The frequencies of DD genotype (0.38) and D allele (0.58) were both higher among the MI group than that among the control group (0.16 and 0.41 respectively,P

The relationship between angiotension converting enzyme gene polymorphism and Binswanger's disease in Chinese / 临床神经病学杂志

Objective To study the relationship between angiotensin converting enzyme (ACE)gene polymorphism and the risk factors of Binswanger's disease (BD) in Chinese Han nationality.Methods ACE gene insertion/deletion(ID) polymorphism in 111 Chinese Han Nationality patients with BD, 98 patients with hypertension and 102 normal controls were detected by polymorase chain reaction (PCR) technology,serum ACE was measured by colorimetric method,the risk factors of BD and family histories were assessed.Results The DD genotype frequency(0.64) was higher in BD group than in hypertension group (0.31, P