The role of aldose reductase gene in the susceptibility to diabetic nephropathy in Type II (non-insulin-dependent) diabetes mellitus

The dinucleotide repeat polymorphism (5'-ALR2) in the promoter region of th e aldose reductase gene on chromosome 7q35 has been implicated in the devel opment of diabetic nephropathy in Type I (insulin-dependent) diabetes melli tus, and markers flanking the aldose reductase locus have given evidence su ggestive of a linkage between diabetic nephropathy and Type II (non-insulin -dependent) diabetes mellitus in Pima Indians. To examine whether the 5'-AL R2 polymorphism in the aldose reductase gene is involved in the development of diabetic nephropathy in Caucasians with Type II diabetes, we carried ou t a large association study. Patients with Type II diabetes from one outpat ient clinic were screened for diabetic nephropathy and divided into three g roups according to the degree of this disease: 179 patients with normoalbum inuria, 225 patients with microalbuminuria and 70 patients with proteinuria . Patients with normoalbuminuria were included in the study only if they ha d had Type II diabetes for 10 or more years. DNA from all patients was geno typed for the 5'-AL-R2 polymorphism using a previously established polymera se chain reaction protocol. The frequency of the putative risk allele Z-2 w as 34.6%, 34.2% and 33.6% in the normoalbuminuria, microalbuminuria and pro teinuria groups, respectively. Similarly no difference among groups was fou nd for the frequency of the putative protective allele Z + 2. In conclusion , the results of our association study in Caucasian patients with Type II d iabetes do not support the hypothesis that the 5'-ALR2 polymorphism in the aldose reductase gene contributes to susceptibility to diabetic nephropathy .