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 t he polyol pathway and is involved in the pathogenesis of diabetic retinopat hy. Polymorphisms of the ALR2 gene are associated with susceptibility to di abetic retinopathy in Chinese and Japanese patients with type 2 diabetes. T here are no reports investigating these polymorphisms in white patients wit h type 1 diabetes from either Western Europe or North America. A CA dinucle otide 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 dia betes, with or without retinopathy. METHODS. The DNA was typed for these polymorphisms using conventional polym erase 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 di abetic retinopathy (n = 159) compared with those without who had diabetes o f 20 years' duration (uncomplicated, n = 70; chi (2) = 17.0, P < 0.0001). T here 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 wi th uncomplicated diabetes. CONCLUSIONS. These results confirm previous studies in other populations an d in type 2 diabetes showing that polymorphisms in the promoter region of t he ALR2 gene are associated with susceptibility to diabetic retinopathy.