Association of an (A-C)n dinucleotide repeat polymorphic marker at the 5′-region of the aldose reductase gene with retinopathy but not with nephropathy or neuropathy in Japanese patients with Type 2 diabetes mellitus

Summary Aims Recently an (A–C)n dinucleotide repeat polymorphic marker in the 5′‐region of the ALR2 gene encoding aldose reductase was found to be associated with diabetic retinopathy in the Chinese population in Hong Kong, and with nephropathy and neuropathy in the British Caucasian population. The present study assessed the association between the polymorphism and microvascular complications in Japanese patients with Type 2 diabetes mellitus. Methods DNA from 87 Japanese patients with Type 2 diabetes mellitus and 90 control subjects with normal glucose tolerance were typed for the polymorphic marker by polymerase chain reaction and direct sequencing. Results Six alleles, namely Z‐12, Z‐6, Z‐4, Z‐2, Z, and Z+2 were identified. There was no significant difference in allele distribution between diabetic patients and controls. The Z‐2 allele frequency was significantly higher in subjects with diabetic retinopathy than those without retinopathy (0.35 vs. 0.20, P = 0.039), suggesting that aldose reductase is involved in the development of diabetic retinopathy. In contrast, the microsatellite marker was not associated with diabetic nephropathy, peripheral or autonomic neuropathy. The discrepancy may be partly attributable to the low frequency of Z+2 allele in the Japanese subjects. Conclusions The (A–C)n dinucleotide repeat polymorphism may be a useful genetic marker to screen for patients at high risk of retinopathy.