Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics

Background: Recent studies suggest that polymorphisms associated to the ald ose reductase gene could be related to early retinopathy in noninsulin depe ndent diabetics (NIDDM). There is also new interest on the genetic modulati on of coagulation factors in relation to this complication. Aim: To look fo r a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)(n) polymorphic marker associated to aldose reductase gene. Patients and methods: A random sample of 27 NIDDM, aged 68.2 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glyc osilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC) (n) polymorphic marker associated to the 5' end of the aldose reductase (AL R2) gene was determined by 32P-PCR plus sequenciation. Mutations of the fac tor XIII-A gene were studied by single stranded conformational polymorphism , sequenciation and restriction fragment length polymorphism. Results: Four patients lacked the (AC)(24) and had a higher rate of appearance of retino pathy than patients with the (AC)(24) allele (0.0167 and 0.0907 score point s per year respectively, p=0.047). Both groups had similar glycosilated hem oglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mut ations were not related to the rate of appearance appearance of retinopathy . Conclusions: Our data suggest that the absence of the (AC)(24) allele of the (AC)(n) polymorphic marker associated to the 5' end of the aldose reduc tase gene, is associated to a five fold reduction of retinopathy appearance rate.