Aldose reductase gene expression is increased in diabetic nephropathy

Area of Science:

• Biochemistry
• Genetics
• Nephrology

Background:

• Insulin-dependent diabetes mellitus (IDDM) with nephropathy shows increased aldose reductase (AR) gene expression.
• Epidemiological studies suggest genetic factors influence the risk for diabetic kidney disease (DKD).
• AR, a key enzyme in the polyol pathway, is a candidate gene for DKD risk.

Purpose of the Study:

• To investigate if AR gene expression is elevated in peripheral blood mononuclear cells of patients with DKD.
• To explore the association between AR gene expression levels and the risk of developing DKD.

Main Methods:

• Peripheral blood mononuclear cells were collected from four groups: normal subjects, IDDM without nephropathy, IDDM with kidney disease, and nondiabetics with kidney disease.
• AR messenger ribonucleic acid (mRNA) levels were quantified using a ribonuclease protection assay.
• AR mRNA levels were normalized to beta-actin mRNA and expressed as molar ratios (AR/beta-actin R).

Main Results:

• AR/beta-actin R was significantly higher in diabetic patients with kidney disease (Group III) compared to normal subjects (Group I) (P < 0.01).
• AR/beta-actin R was also significantly elevated in Group III compared to diabetic patients without kidney disease (Group II) (P < 0.01) and nondiabetics with kidney disease (Group IV) (P < 0.001).
• Nondiabetic patients with kidney disease (Group IV) exhibited significantly lower AR/beta-actin R than normal subjects (Group I) (P < 0.01).

Conclusions:

• The study findings support the hypothesis that elevated AR gene expression is associated with an increased risk of DKD.
• The degree of AR gene expression may play a role in modulating the risk for kidney disease in diabetes mellitus.
• AR gene expression levels could serve as a potential biomarker for DKD risk assessment.