title: ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus.
abstract: BACKGROUND
  ACE polymorphism, especially genotype DD or D allele, may be involved in the progression of diabetic nephropathy. It may also have different effects on the reduction of proteinuria by ACE inhibitors in patients with proteinuria. We investigated the relationship between ACE gene polymorphism and antiproteinuric effect of ACE inhibitors (Benazepril 10 mg/day or Perindopril 4 mg/day) in 83 NIDDM patients with overt proteinuria (urinary protein excretion over 500 mg/day).
  
  
  METHODS
  We recruited NIDDM patients with overt proteinuria from our renal clinic. Before entry, previously used ACE inhibitors were withdrawn for at least 2 weeks and baseline proteinuria and albuminuria were measured. Patients were classified into three groups in accordance with ACE genotypes (17 DD; 33 ID; 33 II) and prospectively followed up for 3 months. Various clinical parameters including age, DM duration, body mass index (BMI), 24-h urine sodium, protein and albumin, BUN, serum creatinine, creatinine clearance (Ccr), mean arterial pressure (MAP), and HbA(1c) were measured in the pre- and post-treatment periods. ACE genotypes were determined by polymerase chain reaction.
  
  
  RESULTS
  There were no significant differences in the clinical parameters such as age, DM duration, BMI, BUN, serum creatinine, Ccr, MAP, HbA(1c), and daily urinary excretion of sodium, protein and albumin among three groups (P>0.05). After the 3-month treatment period using ACE inhibitors, there were no significant differences in the reduction of MAP and Ccr among the three groups (P>0.05). However, the percentage reductions in urinary excretion of protein and albumin for DD genotype were significantly higher than in ID and II genotypes (50.9+/-19.2% vs 19.2+/-16.0%, 20.2+/-20.4%; 52.6+/-23.6% vs. 13.5+/-51.8%, 24.8+/-23.9%, P<0.05). There were no statistically significant correlations between the levels of baseline proteinuria and albuminuria and the magnitudes of the reduction of proteinuria and albuminuria under ACE inhibition (P>0.05).
  
  
  CONCLUSIONS
  Our results suggest that the ACE gene polymorphism might have a role in determining the responsiveness to the antiproteinuric effect of ACE inhibition in proteinuric NIDDM patients.
authors.affiliation: Department of Internal Medicine, Yongdong Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Ha
authors.forename: S
authors.initials: S
authors.lastname: Yong Lee
authors.forename: H
authors.initials: H
authors.lastname: Su Park
authors.forename: J
authors.initials: J
authors.lastname: Ho Shin
authors.forename: S
authors.initials: S
authors.lastname: Jung Kim
authors.forename: D
authors.initials: D
authors.lastname: Hun Kim
authors.forename: K
authors.initials: K
authors.lastname: Rae Kim
authors.forename: H
authors.initials: H
authors.lastname: Yung Lee
authors.forename: D
authors.initials: D
authors.lastname: Suk Han
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020913:Perindopril / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology* / Q000652:urine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D007703:Peptidyl-Dipeptidase A; C044946:benazepril; D020913:Perindopril