The first polymorphisms in the AKR1B1 gene were identified in 1993 (54). A number of additional polymorphisms have been identified in the AKR1B1 gene. Of particular interest has been the (AC)« microsatellite dinucleotide repeat sequence polymorphism in the 5' region of the gene. This dinucleotide repeat polymorphism designated 5' ALR2 is located approximately 2.1 kb upstream of the initiation site of ALR2 close to the ORE sequences. A C-106T SNP situated in the basal promoter region of the ALR2 gene has also been studied, as well as a A(+11842)C SNP within intron 8. Finally, a C(-12)G SNP has also been reported (55).

Table 3

Functional Gene Studies in Diabetic Neuropathy






Neurotrophin-3 VEGF


Insulin-like growth factor-1

Nerve growth Factor Neuropeptides substance P Calcitonin gene-related peptide Adipocytokines (tumor necrosis factor-a, adiponectin, and leptin) Activating transcription factor 3

Increase Increase Increase Increase Increase Increase Delayed expression Decrease

Affect nerve conduction velocity

Increased in neurons

Sciatic nerve in rats Sensory nerve in rats

Responsible for the delay in NGF response in diabetic rats

T2DM with neuropathy

STZ mice

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