Aldose reductase gene polymorphisms and susceptibility to microvascular complications in Type 2 diabetes

The gene encoding the human aldose reductase, the first and rate-limiting enzyme of the polyol pathway of glucose metabolism, is a promising candidate gene which may contribute to diabetic microvascular complications. We investigated the association of two previously reported DNA sequence variants of this gene, the C-106T polymorphism and the (CA)(n) dinucleotide repeat marker, with the risk of albuminuria and retinopathy in Finnish Type 2 diabetic patients and non-diabetic control subjects.

The study population included 85 Finnish, middle-aged, newly diagnosed Type 2 diabetic patients and 126 non-diabetic control subjects. Genetic analyses were performed using the polymerase chain reaction, restriction fragment length polymorphism, and automated laser fluorescence scanning analyses. Microvascular complications were determined using 10-year follow-up data of urinary albumin excretion measurements and ophthalmological examinations.

The C and Z-2 alleles of the C-106T polymorphism and the (CA)(n) repeat marker, respectively, were found to be more frequent in Type 2 diabetic subjects than in non-diabetic subjects. The C and Z-2 alleles were in 60% linkage disequilibrium in diabetic subjects. At the time of diagnosis, diabetic subjects with the T allele of the C-106T polymorphism had significantly higher urinary albumin excretion rate and prevalence of albuminuria than subjects with the C-106C genotype (prevalence of albuminuria: 33.3 vs. 13.8%, P = 0.036, odds ratio = 3.9, 95% confidence interval 1.1, 14.7). The Z-2 allele of the (CA)(n) repeat marker was not consistently associated with the prevalence of albuminuria. No associations were observed between the polymorphisms examined and the prevalence of retinopathy at any point of the follow-up.

The present study suggests that the C-106T polymorphism of the aldose reductase gene could be involved in the early development of microalbuminuria in Finnish Type 2 diabetic patients.