Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes

Area of Science:

• Genetics
• Diabetology
• Neurology

Background:

• Diabetic neuropathy is a significant complication of type 2 diabetes.
• The role of genetic factors, specifically aldose reductase (ALR) gene variants, in diabetic neuropathy progression is not fully understood.
• Previous studies have suggested associations between ALR gene polymorphisms and diabetic complications.

Purpose of the Study:

• To screen the human aldose reductase (ALR) gene for DNA sequence variants in type 2 diabetic and nondiabetic individuals.
• To investigate the association between identified ALR gene polymorphisms and neurophysiologic deterioration and clinical peripheral neuropathy.

Main Methods:

• Genetic screening of 85 Finnish type 2 diabetic and 126 nondiabetic subjects using PCR and various genotyping techniques.
• Detailed neurologic examinations and neurophysiologic analyses (nerve conduction studies) were conducted at baseline and after 10 years.
• Statistical analysis to determine associations between ALR gene polymorphisms and neurophysiologic parameters.

Main Results:

• Four ALR gene polymorphisms were identified: C-106T, C-11G, A11370G, and C19739A.
• The C-106T polymorphism's C and Z-2 alleles and a (CA)(n) repeat marker were more prevalent in type 2 diabetic subjects.
• Diabetic individuals with the C-106T polymorphism's T allele exhibited lower sensory nerve amplitudes and a greater decrease in motor peroneal nerve conduction velocity over time, but no association with clinical polyneuropathy was found.

Conclusions:

• The C-106T polymorphism in the aldose reductase (ALR) gene may contribute to the early development of neurophysiologic deterioration in type 2 diabetic patients.
• This specific genetic variant could serve as a biomarker for predicting nerve function decline in individuals with type 2 diabetes.