Angiotensin converting enzyme gene polymorphism and renal hemodynamic function in early diabetes

Area of Science:

• Nephrology
• Genetics
• Endocrinology

Background:

• The angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects circulating ACE levels.
• Previous studies suggest a link between the ACE I/D polymorphism and diabetic nephropathy risk in insulin dependent diabetes mellitus (IDDM) patients.
• Early increases in glomerular filtration rate (GFR) are a potential risk factor for diabetic nephropathy.

Purpose of the Study:

• To investigate whether the ACE I/D polymorphism influences renal hemodynamic function in patients with uncomplicated IDDM.
• To determine if differences in renal hemodynamics explain the protective effect of the ACE I allele against diabetic nephropathy.

Main Methods:

• Genomic DNA was analyzed for the ACE I/D polymorphism using polymerase chain reaction in 39 IDDM patients and 20 controls.
• Renal hemodynamic parameters, including GFR and effective renal plasma flow (ERPF), were measured using clearance techniques.
• Blood glucose levels were strictly controlled in IDDM patients using a modified euglycemic clamp technique.

Main Results:

• Patients homozygous for the ACE I allele exhibited significantly higher mean GFR (143 ml/min/1.73 m2) compared to those homozygous for the D allele (121 ml/min/1.73 m2).
• ERPF was also significantly greater in I allele homozygotes (850 ml/min/1.73 m2) versus D allele homozygotes (672 ml/min/1.73 m2).
• No significant differences were observed in mean arterial pressure, glycosylated hemoglobin, or albumin excretion rates among genotype groups.

Conclusions:

• The ACE gene I/D polymorphism significantly impacts glomerular filtration and renal plasma flow rates in early, uncomplicated IDDM.
• Observed differences in renal hemodynamic function do not appear to account for the protective effect of the ACE I allele against diabetic nephropathy development.