Polymorphisms of the aldose reductase gene and susceptibility to retinopathy in type 1 diabetes mellitus.

PURPOSE Aldose reductase (ALR2) is the first and rate-limiting enzyme of the polyol pathway and is involved in the pathogenesis of diabetic retinopathy. Polymorphisms of the ALR2 gene are associated with susceptibility to diabetic retinopathy in Chinese and Japanese patients with type 2 diabetes. There are no reports investigating these polymorphisms in white patients with type 1 diabetes from either Western Europe or North America. A CA dinucleotide repeat polymorphism (5'ALR2; located at -2100 bp) as well as a novel C(106)T polymorphism was investigated in 229 white patients with type 1 diabetes, with or without retinopathy. METHODS The DNA was typed for these polymorphisms using conventional polymerase chain reaction techniques. RESULTS There was a highly significant increase in the frequency of the Z-2 5'ALR2 allele and Z-2/X (where X is not Z+2) genotype in patients with diabetic retinopathy (n = 159) compared with those without who had diabetes of 20 years' duration (uncomplicated, n = 70; chi(2) = 17.0, P < 0.0001). There was a similar decrease in the Z+2/Y genotype (where Y is not Z-2; chi(2) = 30.1, P < 0.000,001) in the patients with retinopathy compared with the uncomplicated diabetes group. The C/Z-2 C(-106)T/5' ALR2 haplotype was found in 33.3% of the patients with retinopathy and 8.7% of the patients with uncomplicated diabetes. CONCLUSIONS These results confirm previous studies in other populations and in type 2 diabetes showing that polymorphisms in the promoter region of the ALR2 gene are associated with susceptibility to diabetic retinopathy.