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Impact of Angiotensin-Converting Enzyme Gene Polymorphism on Proteinuria and Arterial Hypertension

Marijana Živko ; General Hospital Virovitica, Department of Internal Medicine, Virovitica, Croatia
Rajko Kušec ; University of Zagreb, University Hospital Dubrava, Department for Molecular Diagnostics and Genetics, Zagreb, Croatia
Krešimir Galešić ; University of Zagreb, University Hospital Dubrava, Department of Internal Medicine, Division of Nephrology, Zagreb, Croatia

Puni tekst: engleski pdf 207 Kb

str. 765-770

preuzimanja: 319



Proteinuria is the hallmark of renal disease. In essential hypertension the onset of de novo proteinuria is associated with faster rate of progression of disase. Some authors have suggested that the DD genotype of the angiotensin-convert- ing enzyme (ACE) gene would be an adverse renal prognosis factor. It may also have different effects on the reduction of proteinuria by ACE inhibitors in patients with proteinuria. Observations on the association between the ACE gene poly- morphism and hypertension have been inconsistent, which might be due to ethnic and geographical variations. In this study was to investigated the relationship between ACE gene polymorphism and antiproteinuric effect of ACE inhibitors (ramipril) and to evaluate the possible association between I/D polymorphism and hypertension. We recruited 66 hyper- tensive patients (male 42, female 24) with overt proteinuria (urinary protein excretion over 500 mg/day). Patients were classified into three groups in accordance with ACE genotypes (17 DD; 35 ID; 14 II). They were treated with ramipril and prospectively followed up for one year. Various clinical parameters including age, body mass index (BMI), 24-h urine protein, creatinine, creatinine clearance (Ccr), systolic and diastolic blood pressure (SBP and DBP), mean arterial pres- sure (MAP) were measured in the pre- and post-treatment periods. The ACE gene insertion/deletion(I/D) polymorphisms in intron 16 were determined by PCR. Results showed that there were no significant differences in the clinical parame- ters such as age, gender, serum creatinine, Ccr, SBP , DBP , MAP , and daily urinary excretion of protein among three groups (P>0.05). ID genotype patients were found to have lower BMI (p=0.031). ACE inhibition significantly reduced proteinuria in all genotype groups (p<0.05). The percentage reductions of 24-h urinary excretion of protein were signifi- cantly different between the genotype groups (p=0.042) and for DD genotype were significantly greater than in ID (79.2± 28.9% vs 49.2±64.8%, P=0.015). The slope of SBP was the main factor related to the slope of the percentage reduction of proteinuria, however, a significant negative correlation coefficient between these parameters was found (rs=–0.382, p= 0.002). We failed to find significant difference in outcomes of treatments with ACE inhibitor between male and female ac- cording the I/D polymorphism of the ACE gene. D allele in the ACE genotype could be a useful genetic marker with im- portant clinical, therapeutic and prognostic implications in recognizing patients with proteinuria that are at greater risk of renal damage.

Ključne riječi

ACE-genotype, ACE inhibitors, antiproteinuric effect, arterial hypertension, proteinuria

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