Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy

Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy. Previous studies have shown that the angiotensin-converting enzyme (ACE) gene polymorphism is associated with an increased risk of vascular disease in non-diabetic patients. The present study was conducted on 509 NIDDM patients who underwent a screening test to determine their ACE genotype for the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Various baseline indices were correlated with the three ACE polymorphisms. The genotype was determined through polymerase chain reaction amplification of the angiotensin-converting enzyme polymorphism. The univariate relationship between the presence of the DD genotype with nephropathy as measured by urinary albumin excretion (UAE), and a history coronary artery disease (CAD) was then examined. Finally, a multiple model for each UAE and CAD was created so as to determine the independent effects of the presence of the DD genotype on each diabetic complication. Univariately, the presence of the DD genotype was associated with diabetic nephropathy. Furthermore, in a multiple model predicting diabetic nephropathy, the presence of the DD genotype was independently associated with diabetic nephropathy (odds ratio = 2.8, 95% confidence interval 1.4 to 5.5) but not CAD. Thus, the ACE DD genotype in 509 non-Hispanic white NIDDM patients in a metropolitan area in the U.S. was independently associated with the presence of diabetic nephropathy and, therefore, may be potentially used as a marker for NIDDM patients at risk for developing diabetic nephropathy

901-94 The Angiotensin Converting Enzyme DD Genotype is Associated with Preserved Right Ventricular Function in Patients with Severe Primary Pulmonary Hypertension

A polymorphic marker within the ACE gene has been found to correlate with circulating and tissue ACE activities and with the incidence of severe pulmonary hypertension (Abraham et al, JACC 1994; 23: 177A). While the association of the ACE DD genotype and pulmonary hypertension suggests a role for angiotensin II (Ang II) in the pulmonary vasoconstriction and pulmonary vascular smooth muscle proliferation characteristic of this disorder, we hypothesize a compensatory role for Ang II in the maintenance of right ventricular (RV) function in such patients. We evaluated the frequency of the ACE DD genotype in 55 patients with severe primary pulmonary hypertension (PPH) and compared clinical severity and right heart hemodynamics at the time of presentation in 20 of these patients stratified on the basiw of their ACE genotype (DD vs non-DD, n=10 in each group). The incidence of the ACE DD genotype was 49% in the PPH patients compared to 23% in a control population (n=89, p=0.0009). Mean±SEM right heart hemodynamics, echocardiographic RV internal dimensions (RVID) and NYHA classifications for the 2 groups are shown below: DDNon-DDp valueMean PA Pressure (mmHg)52±453±30.84PCWP (mmHg)5±16±10.59Cardiac Output (L/min)5.12±0.432.65±0.210.00007PVR (Wood Units)10.0±1.319.3 ±2.40.004RA Pressure (mmHg)5±110±20.08RVID(cm)3.1±0.33.7±0.20.08NYHA Class2.2±0.33.3±0.20.02Significantly, the duration of symptoms attributable to PPH was not different between the DD and non-DD groups (35±19 vs 22±6 months, p=0.58). Conclusion: The ACE DD genotype is associated with preserved RV function in PPH patients, supporting a compensatory myocardial or inotropic role for Ang II in PP

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The Arctic

International audienc