An aldose reductase intragenic polymorphism associated with diabetic retinopathy

The polyol pathway has been considered important in the development of diabetes long-term complications. Diabetic patients with microvascular disease have increased gene expression and enzyme activity, which may be due to variants in the aldose reductase gene. An association of an intragenic BamHI polymorphic site with diabetic retinopathy and nephropathy has been suggested, but the BamHI site has not been confirmed. In the current study, long template PCR-RFLP and DNA sequencing were used to ascertain its existence. A single substitution of A to C at 95th nucleotide of intron 8 was identified. This polymorphism was investigated in 164 adolescents with type 1 diabetes in whom diabetic retinopathy was assessed by stereoscopic retinal photography. Both the wild haplotype B and homozygote BB were significantly more common in the adolescents with retinopathy than in those without retinopathy (P = 0.018 and 0.002, respectively). We also confirmed an association between a previously described (CA)n repeat sequence and retinopathy in these adolescents (P < 0.0005). However, there was no association between the two polymorphisms.