Aldose reductase gene polymorphism is associated with progression of diabetic nephropathy in Japanese patients with type 1 diabetes mellitus

Diabetes Obes Metab. 2003 Jan;5(1):51-7. doi: 10.1046/j.1463-1326.2003.00243.x.


Aim: The objective of this study was to investigate cross-sectionally and longitudinally whether polymorphism of the (A-C)n dinucleotide repeat sequence of the aldose reductase (AR) gene may modulate risk for diabetic nephropathy or retinopathy in Japanese patients with type 1 diabetes.

Methods: We obtained DNA samples from 101 patients followed up after the onset of type 1 diabetes and analysed a (A-C)n dinucleotide repeat polymorphic marker in the AR gene by polymerase chain reaction (PCR) method.

Results: Ten alleles ranging from Z-10 (128 bp) to Z+8 (146 bp) in repeat number were identified. In cross-sectional studies, the prevalence of the Z+2 allele was higher than that of any other allele in patients with diabetic nephropathy (37.5% of patients in a microalbuminuria group, and 41.7% of those in a macroalbuminuria group including patients with chronic renal failure and maintenance haemodialysis treatment). Prevalence of the Z+2 allele was not increased in patients with diabetic retinopathy. In longitudinal Kaplan-Meier plots, the cumulative incidence of nephropathy was significantly associated with homozygosity for the Z+2 allele (log rank test, p = 0.031); respective prevalence of nephropathy after diabetes durations of 10 and 15 years was 42.9% and 100% in Z+2 homozygotes (n = 8), 17.6% and 27.4% in Z+2 heterozygotes (n = 44), and 6.1% and 17.4% in patients without the Z+2 allele (n = 49). However, occurrence of retinopathy was not influenced by the Z+2 allele (log rank test, p = 0.926).

Conclusions: Homozygosity for the Z+2 allele was associated with accelerated early progression of diabetic nephropathy in Japanese type 1 diabetic patients.

MeSH terms

  • Adult
  • Aldehyde Reductase / genetics*
  • Alleles
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetic Nephropathies / genetics*
  • Diabetic Retinopathy / genetics*
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polymorphism, Genetic*


  • Aldehyde Reductase