A meta-analysis on the association of genetic polymorphism of the angiotensin-converting enzyme and coronary artery disease in the chinese population

SUMMARY OBJECTIVE: To investigate the association between genotype insertion or deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and susceptibility to coronary artery disease (CAD) in Chinese Han population. METHODS: We conducted a comprehensive search for the OR value of contrast between the group of genotype insertion or deletion polymorphism of the ACE and the group of CAD as an effective index. A meta-analysis (Stata 12.0) was used to test the heterogeneity of the results, combine the values for effect, conduct sensitivity analysis, and basic evaluation. RESULTS: A total of 638 studies were found on the association between polymorphisms of the angiotensin-converting enzyme gene and CAD, of which 44 studies met the inclusion criteria. In total, our study included 5619 cases and 4865 controls. The heterogeneity test of each study (P < 0.001) was carried out using a random effect model. The OR value of DD/ID+II was 1.95, 95% confidence interval (95%CI) (1.66-2.29). The OR value of II/DI+DD was 0.63, 95%CI (0.55-0.72). The funnel figure is basically symmetrical and the results of the sensitivity analysis were stable. CONCLUSION: The DD genotype of the angiotensin converting enzyme gene may be a weaker risk factor for CAD in the Chinese Han population.

RESUMO OBJETIVO: Investigar a associação entre o polimorfismo de inserção ou deleção do genótipo do gene da enzima conversora da angiotensina (ACE) e a susceptibilidade da etnia Han chinesa para a doença arterial coronariana (DAC). Métodos: Foi realizada uma pesquisa abrangente para o valor de OR (Odds Ratio) de contraste entre o grupo de polimorfismo de inserção ou deleção do genótipo do gene da enzima conversora da angiotensina (ACE) e o grupo de doença arterial coronariana (DAC) como um índice de eficácia. Uma meta-análise (Stata 12,0) foi utilizada para testar a heterogeneidade dos resultados, combinar os valores de eficácia, realizar análises de sensibilidade e de avaliação básica. RESULTADOS: Um total de 638 estudos foram encontrados sobre a associação entre polimorfismos do gene da enzima conversora da angiotensina e doença arterial coronariana, dos quais 44 satisfaziam os critérios de inclusão. Nosso estudo incluiu 6246 casos e 5713 controles. O teste de heterogeneidade de cada estudo (p < 0,001) foi realizado seguindo o modelo de efeito randômico. O valor de OR para DD/ID+II foi 1,95, com 95% de intervalo de confiança de (95%CI) (1,66-2,29). O valor de OR para II/DI+DD foi 0,63, com 95% IC (0,55-0,72). A figura do funil é basicamente simétrica e os resultados da análise de sensibilidade foram estáveis. CONCLUSÃO: O genótipo DD do gene da enzima conversora da angiotensina podem ser um fator de risco mais fraco para doença coronariana na população chinesa Han.

The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients

ABSTRACT Objectives This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.3% vs. 12.0%; ID: 37.8% vs. 37.3; DD: 48.9% vs. 50.7%; CC: 36.2% vs. 39.0%; CT: 46.8% vs. 49.3%; TT: 17.0% vs. 11.7%), and alleles (I: 32.2% vs. 30.7%; D: 67.8% vs. 69.3%; C: 59.6% vs. 63.6%; T: 40.4% vs. 36.4%) and their synergisms in the pathophysiology of T2DM. On analyzing the T2DM Group, there were no significant differences in the presence of complications. In this population of Brazilian obese patients, no correlation was found between the ACE and MTHFR polymorphisms in the development of T2DM. Conclusion Analyzing only the group with diabetes, there was also no relationship between these polymorphisms and comorbidities.

Insertion/deletion polymorphism of ACE gene in females with peripartum cardiomyopathy: A case-control study

Background The role of polymorphism of Angiotensin converting enzyme (ACE) gene and ACE activity in etiopathogenesis, prognosis, and many other clinical parameters in the various form of the cardiovascular disease has been established to some degree of certainty. The pathophysiology of Peripartum cardiomyopathy (PPCM) remains an area of active research. The main aim of our study was to see pattern of ACE- Insertion/Deletion (I/D) allele in PPCM and its implications on left ventricular performance indices. Methods This single-center case-control study included 45 cases and 70 controls. The diagnosis of PPCM was established clinically and echocardiographically. ACE genotyping was done by polymerase chain reaction (PCR) method in all subjects. Results The II, ID, and DD genotype was present in 16, 18 and 11 of subjects with PPCM and 48, 19 and 3 of controls respectively. The odds ratio for ACE-II genotype in cases vs. controls was 0.253 (95% CI = 0.114–0.558; p = 0.007), for that of II genotype was 1.93 (95% CI = 0.86–4.3; p = 0.107) and for DD genotype was 7.225 (95% CI; 1.88–27.6; p = 0.0039). Overall frequency of D allele in cases was significantly higher than controls (odds = 4.25; 95% CI = 2.01–6.7; p = 0.0001). Moreover, ejection fraction, left ventricular volume and linear dimensions were worse in patients with DD genotype. Conclusion ACE DD genotype and overall frequency of D allele is significantly higher in patients with PPCM. Also, the presence of DD genotype is associated with worse systolic performance indices measured echocardiographically.

Polimorfismo inserción/deleción del gen de la enzima convertidora de angiontensina y enfermedad coronaria en la población de Montería, Córdoba / Insertion/deletion polymorphism of the angiotensin converting enzyme gene and coronary artery disease in the population of Monteria, Cordoba

Antecedentes y objetivo: el polimorfismo inserción/deleción del gen de la enzima convertidora de angiotensina, ha sido identificado como un potente factor de riesgo de enfermedad coronaria. Para la población de Montería se desconocen las frecuencias con las que se expresan los alelos de este gen y el carácter de su interacción con condiciones de riesgo cardiovascular. El objetivo de este trabajo fue determinar, para dicha población, la asociación de este polimorfismo y el riesgo de sufrir enfermedad coronaria. Método: se llevó a cabo un estudio retrospectivo con 70 casos y 70 controles; como casos se consideraron pacientes con padecimientos coronarios confirmados por electrocardiograma, remitidos a la Organización Cardiodiagnóstico de Córdoba, y como controles individuos voluntarios sin antecedentes cardiovasculares y sin relación filial. El ADN requerido se extrajo a partir de sangre periférica. La caracterización del polimorfismo se hizo mediante reacción en cadena de la polimerasa. Resultados: la distribución de genotipos de la enzima convertidora de angiotensina en pacientes casos no fue significativamente diferente a la estimada en pacientes controles (X2=3.687, p=0,1583). El genotipo más frecuente en la población fue ID (40,72%). En el grupo casos, el genotipo II fue más frecuente que el genotipo DD comparado con el grupo control (p<0,05). El modelo de regresión logística múltiple ajustado, indicó no significancia del genotipo DD como factor de riesgo coronario (razón de disparidad = 0,51 IC95% = 0,25 – 1,06). Conclusión: el polimorfismo I/D del gen de la enzima convertidora de angiotensina no mostró ser un factor de riesgo significativo para enfermedad coronaria en la población de Montería.

Background and Objective: the insertion/deletion polymorphism of the gene for angiotensin converting enzyme has been identified as a potent risk factor for coronary heart disease. For the population of Monteria, the frequency with which the alleles of this gene are expressed and the nature of its interaction with cardiovascular risk conditions, are not known. The aim of this work was to determine the association of this polymorphism and the risk of coronary heart disease in this population. Methods: a retrospective study of 70 cases and 70 controls was conducted. Cases were the patients with coronary disease confirmed by electrocardiogram , reported to the Cordoba Cardiodiagnosis Organization and the control ones were volunteers without history of cardiovascular disease and without filial relationship. Required DNA was extracted from peripheral blood. Polymorphism characterization was done by the polymerase chain reaction. Results: the distribution of genotypes of the angiotensin converting enzyme gene in patients cases was not significantly different from that estimated in control patients (X2 = 3.687, p = 0.1583). The most common genotype in the population was ID (40.72%). In the group cases, genotype II was more frequent than the DD genotype compared with the control group (p < 0,05). The multiple logistic regression adjusted model indicated no significance of DD genotype as coronary risk factor (odds ratio = 0.51 95% CI = 0.25 to 1.06). Conclusion: I/D polymorphism of the angiotensin converting enzyme gene did not show to be a significant risk factor for coronary heart disease in the population of Monteria.

Relationship between diabetic retinopathy and angiotensin converting enzyme gene deletion polymorphism: a systemic review / 中华内分泌代谢杂志

To clarify the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and diabetic retinopathy in type 2 diabetic patients by meta analysis. 16 eligible articles were selected in this study, including 1 014 patients with diabetic retinopathy and 1 135 controls. The meta analysis revealed that systematic data Z= 2.91 ( P = 0.004 ), OR = 1.69 ( 95% CI 1.19-2.40). There is association between ACE gene I/D polymorphism and the diabetic retinopathy in type 2 diabetic patients.

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 relation between angiotensin converting enzyme (ACE) gene polymorphism and neonatal hyperbilirubinemia in Korea / 소아과

PURPOSE: Human angiotensin converting enzyme (ACE) gene shows an insertion/deletion polymorphism in 16 intron, and three genotypes are determined by whether a 287 bp fragment of the DNA is present or not; II, ID and DD genotype. DD genotype has been suggested as a risk factor of chronic nephrotic disease such as IgA nephropathy and diabetic nephropathy, various cardiovascular diseases and several other diseases. ACE activity increases in acute hepatitis, chronic persistent hepatitis, chronic active hepatitis and cirrhosis. On the other hand, patients with fatty livers have normal ACE activity. This study was designed to find out the relation between polymorphsims of the ACE genes and neonatal hyperbilirubinemia in Koreans. METHODS: The genomic DNA was isolated from 110 full-term Korean neonates who had hyperbilirubinemia with no obvious causes (serum bilirubin?12 mg/dL) and 164 neonates of a control population (serum bilirubin?12 mg/dL). We performed polymerase chain reaction (PCR) to see the allele of the ACE gene. Electrophoresis was done in the PCR products in 1.5 percent agarose gel, and then DNA patterns were directly visualized under ethidium bromide staining. RESULTS: ACE genotypes in the hyperbilirubinemia group are as follows; 26.36 percent for II, 53.64 percent for ID, 20.00 percent for DD, 0.532 for I allele and 0.468 for D allele. These distributions were not significantly different from those in the control group; 24.39 percent for II, 51.83 percent for DI, 23.78 percent for DD, 0.503 for I allele and 0.497 for D allele. CONCLUSION: In this study, ACE gene polymorphism was detected in the neonatal hyperbilirubinemia and control group. The most frequent genotype was ID. Our results indicate that the ACE gene polymorphism is not associated with the prevalence of neonatal hyperbilirubinemia in Koreans.

Association between Left Ventricular Hypertrophy (LVH) and Angiotensin Converting Enzyme (ACE) Gene Polymorphism in Diabetic Nephropathy Patients / 대한신장학회잡지

BACKGROUND: Left ventricular hypertrophy (LVH) is an important risk factor of cardiovascular disease in diabetic nephropathy patients. Renin-angiotensin system has an independent role as a neurohormonal factor in promoting cardiac growth and remodeling. Genetic and environmental factors also influence the pathogenesis of LVH. The association of LVH progression and angiotensin converting enzyme (ACE) gene polymorphism is well known, especially in ACE DD genotype. But there is some controversy between LVH and ACE gene polymorphism. So, we evaluated the prevalence and patterns of LVH and analyzed the associated factors including ACE polymorphism in diabetic nephropathy patients. METHODS: One hundred and eighty one type 2 diabetic patients with overt proteinuria were recruited in the study. ACE genotyping and echocardiogram were performed to observe the association between LVH and ACE polymorphism. RESULTS: The prevalence of LVH was 141 out of 181 (77.9%) patients (concentric, 35.9% and eccentric, 42.0%, each). Patterns of LVH, left ventricular mass (LVM), and left ventricular mass index (LVMI) showed no differences among the three genotypes. But, LVMI was higher in DD genotype group than in II group in men (171.2 vs. 144.8, p=0.028). On the other hand, in women, there were no differences of clinical and echocardiographic variables among three genotypes. LVM and LVMI were negatively correlated with hemoglobin level in all patients. CONCLUSION: The results suggest that ACE DD genotype is associated with LVH in male patients with diabetic nephropathy, but not in female patients. Determining whether or not the gender influences LVH in the diabetic nephropathy patients will require further studies.

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.

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism in Korean Patients with Rheumatoid Vasculitis / 대한류마티스학회지

OBJECTIVE: Rheumatoid arthritis has various extra-articular manifestations including rheumatoid vasculitis. Angiotensin converting enzyme (ACE) gene shows insertion/deletion polymorphism and has II, ID, DD genotypes. ACE gene is related with vasoconstriction and endothelial dysfunction in cardiovascular disease. This study was undertaken to determine the association between ACE gene polymorphism and rheumatoid vasculitis. METHODS: Twenty-nine patients were collected as rheumatoid vasculitis group. DNA was isolated from blood samples collected from 114 Korean rheumatoid arthritis patients meeting American College of rheumatology 1987 revised criteria, and 114 healthy control group. Genotyping for the angiotensin converting enzyme gene insertion/deletion polymorphism was performed by polymerase chain reaction method. RESULTS: As vasculitis manifestation, 15 patients showed neuropathy, 13 showed scleritis, 3 showed skin rash. In rheumatoid vasculitis group, II, ID and DD polymorphism was seen in 8 (27.6%), 15 (51.7%), 6 (20.7%) patients respectively and 39 (34.2%), 57 (50.0%), and 18 (15.8%) in normal controls. There was no skewing of ACE I/D polymorphism in compared with normal group. In rheumatoid arthritis control group, II, ID and DD polymorphism was seen in 37 (32.5%), 64 (56.1%), and 13 (11.4%) patients. Among rheumatoid arthritis patient, there was no significant difference between patient with vasculitis and without vasculitis. CONCLUSION: Our results showed that genetic polymorphisms of angiotensin converting enzyme insertion/deletion gene has no association with the susceptibility to rheumatoid vasculitis.

Lack of Association between an Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Allergic Rhinitis in a Korean Population

BACKGROUND AND OBJECTIVES: Angiotensin -converting enzyme (ACE) inactivates bradykinin, substance P, and neurokinin A, which are thought to play important roles in the pathogenesis of inflammatory diseases. An insertion/deletion (I/D) poly - morphism in the ACE gene was reported to be associated with atopy in a Czech population. MATERIALS AND METHODS: Using the polymerase chain reaction, we investigated the frequencies of the genotypes and alleles of the ACE gene in 137 patients with allergic rhinitis and 498 healthy control subjects. RESULTS: There was no difference in the frequencies of the genotypes in the controls and patients with allergic rhinitis (p>0.05). The D allele was more frequent in patients with allergic rhinitis, but the difference was not statistically significant (p>0.05). CONCLUSION: Our results indicate that I/D polymorphism in the ACE gene is not related to susceptibility to allergic rhinitis in the Korean population.

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.

The Effect of Angiotensin Converting Enzyme Gene Polymorphism in Children with Henoch-Schonlein Purpura Nephritis

PURPOSE: Henoch-Schonlein purpura(HSP) nephritis has been reported to vary from 25 to 50% among HSP patients and is a common cause of chronic glomerulonephritis in children. In our study, we evaluated the distribution and the association of the Insertion/Deletion(I/D) polymorphism of angiotensin converting enzyme(ACE) gene with clinical manifestations, particularly proteinuria in children with HSP nephritis, compared with that in HSP. METHODS: ACE gene polymorphism was determined in children with HSP nephritis(n=33) and HSP(n=28) who were diagnosed in Busan Paik hospital from January 1996 to June 2001. The I/D polymorphism of ACE gene was determined by PCR amplication of genomic DNA. RESULTS: The ACE I/D genotype frequency was DD : 25%, ID : 50%, II : 25% in HSP and DD : 24 %, ID : 46%, II : 30% in HSP nephritis, there was no significant difference in the genotype and allele frequencies between two groups. When statistical analysis was done according to the presence of D allele, the amount of 24-hour urinary protein excretion and the incidence of moderate to heavy proteinuria(>500 mg/m2/day) at onset and last follow-up were higher in DD/ID genotype than in those in II genotype, but these differences were not statistically significant. CONCLUSION: We suggest a lack of association between I/D polymorphism of ACE gene and clinical manifestations in children with HSP nephritis. However, further follow-up studies based on a sufficient number of patients and long term follow up periods are necessary to confirm the role of I/D polymorphism of ACE gene in children with HSP nephritis.

Relationship between the polymorphism of angiotensin converting enzyme gene and vascular complications in type 2 diabetes in Guangxi region / 中国实用内科杂志

Objectives To investigate the relationship between the insertion and deletion (I/D) polymorphism of human angiotensin converting enzyme (ACE) gene and the vascular complications in type 2 diabetes. Methods The I/D polymorphism of ACE gene was detected by polymerase chain reaction in 120 type 2 diabetic patients and 100 healthy controls. Results The frequency of DD genotype was significantly higher, while frequency of II genotype was lower in diabetic nephropathy patients (DN) than those in control group. The frequency of ID genotype was significantly higher, while frequency of II genotype was lower in type 2 diabetic patients with coronary heart disease (CHD), when compared to those without CHD. The frequencies of ACE genotypes in patients with diabetic retinopathy (DR) or hypertension (HP) were not different from those in control group and non-DR or non- HP patients. Conclusions ① There were relationships between the I/D polymorphism of ACE gene and DN and CHD in type 2 diabetes. ② The DD genotype and D allele of ACE gene might be as markers in predisposing DN, while II genotype and I allele as protective factors for DN in diabetes. The ID genotype might be as a marker in predisposing CHD, while II genotype as a protective factor for CHD in diabetes.③ There was no relationship between I/D polymorphism of ACE gene and HP or DR in diabetes in Guangxi region.

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

Gene Ploymorphisms of Angiotensin Converting Enzyme and Endothelial Nitric Oxide Synthase in Patients with IgA Nephropathy / 대한신장학회잡지

To evaluate the association between ACE gene I/D polymorphism and ecNOS gene a/b polymorphism in IgA nephropathy, 158 IgA nephropathy patients and 121 control subjects were examined. In genotype distribution of the ACE gene I/D polymorphism, there was no significant difference in genotype distribution between controls and IgA nephropathy patients. We also examined the association between ACE genotype and clinical characteristics in the patients with IgA nephropathy. The incidence of hypertension in patients with DD genotype was higher than that of other genotypes. There were no significant association between I/D polymorphism distribution and chronic renal failure, nephrotic range proteinuria, and glomerular sclerosis in IgA nephropathy. In genotype distribution of ecNOS gene a/b polymorphism, there was no significant difference between IgA nephropathy patients and controls. There was no significant difference in frequency of chronic renal failure, hypertension, nephrotic range proteinuria and glomerular sclerosis among ecNOS genotypes. In addition, we failed to detect any significant association between the ACE and ecNOS gene-polymorphis ms and the decline of renal function in IgA nephropathy. A further study with larger number of patient population would be necessary.

Angiotensin Converting Enzyme Gene Polymorphism in Patients with Minimal Change Nephrotic Syndrome and Focal Segmental Glomerulosclerosis / 대한신장학회잡지

Angiotensin converting enzyme gene insertion/ deletion polymorphism has been shown to be associated with cardiovascular disease including cardiomyopathy, myocardial infarction, essential hypertension, progression of IgA nephropathy and diabetic nephropathy. Since glomerulosclerosis has similarities to atherosclerosis, angiotensin converting enzyme gene polymorphism may be associated with glomerulsclerosis. Therefore, we tested whether genotype distribution of the insertion/deletion polymorphism in angiotensin converting enzyme gene is different in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis. In genotype distribution of the angiotensin converting enzyme gene I/D polymorphism, control subjects were II type 44.3%, ID type 40.9%, DD type 14.8% and patients with minimal change nephrotic syndrome were II type 38.2%, ID type 45.5%, DD type 16.3% and patients with focal segmental glomerulosclerosis were II type 13.3%, ID type 46.7%, DD type 40.0%. This result suggests that DD genotype was more frequent in patients with focal segmental glomerulosclerosis than minimal change nephrotic syndrome and control subjects. We also examined the association between ACE genotype and clinical characteristics in the patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis. There were no significant association between I/D polymorphism distribution and hypertension, chronic renal failure, response to steroid in patients with minimal change nephrotic syndrome. The incidence of chronic renal failure in patients with focal segmental glomerulosclerosis DD genotype was higher than that of other genotypes. The response rate to steroid in patients with focal segmental glomerulosclerosis DD genotype was lower than that of other genotypes.

A Common Genetic Variant of the Angiotensin Converting Enzyme(ACE) Gene and Pregnancy InducedHypertensive Disorders / 대한산부인과학회잡지

BACKGROUND: The angiotensin coverting enzyme(ACE) gene(encoding kininase II, EC3.4.15.1) contains a polymorphism based on the presence(insertion [I]) or absence(deletion[D]) within an intron of a 287bp nonsense DNA domain, resulting in three genotypes(D/I) and I/I homozygotes, and I/D heterozygotes). Alu insertion is associated with lowerACE level than deletion allele(D) and it was observed that D/D individuals have twice theACE activity of I/I patients. Pregnancy induced hypertension(PIH) probably results fromdominating pressor systems owing to loss of antagonizing vasodilator autacoids. AngiotensinII is an extremely potent arteriolar vasoconstrictor. Overactivity or failure to supressresponsiveness to the increased activity of angiotensin II, which is generated by ACE,would seem to be a reasonable basis for the vasoconstriction of PIH. The aim of this studyis to evaluate the relationship between ACE genotype and PIH. METHODS: Blood sampling was taken from 39 patients with PIH. The hypertensivedisorders, confirmed at postpartum follow up, were classified as gestational hypertensionwithout proteinuria, preeclampsia(mild and severe) and eclampsia. The diagnosis ofpreeclampsia was made according to the American College of Obstetrics and Gynecology criteriaof hypertension and proteinuria(>300 mg/24 hr urine). Genomic DNA was extractedfrom blood sample. After PCR amplification of the respective fragments from intron 16 ofthe ACE gene, size fractionation and visualization by electrophoresis were performed. RESULTS: PIH group(including gestational hypertension, mild and severe preeclampsia: frequency of I allele 0.756 and D allele 0.244) had more I allele and less D allele whencompared with normal population(frequency of I allele 0.609 and D allele 0.391)(p < 0.05).And PIH group had more I/I homozygote individuals showing significant distortion fromHardy-Weinberg equilibrium of ACE genotype(p < 0.05). Moreover, severe preeclampsiagroup alon(frequency of I allele 0.759 and D allele 0.241) had more I allele and less Dallele when compared with normal population and had significantly more I/I homozygoteindividuals. CONCLUSION: As pregnancies with PIH had more ACE I allele and I/I homozygoteindividuals. PIH could be associated with I allele of the ACE gene. Considering the observedcodominant association between the D-I polymorphism and plasma ACE activity, our resultis in favor of the thesis that PIH primarily arises from defective synthsis of vasodilatingautacoids and renin-angiotensin system exerts secondary vasoconstrictive action. However,the relationship between ACE genotype and defective vasodilating mechanism during pregnancyis unknown at present.

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