GENETIC-FACTORS, NA K ATPASE ACTIVITY AND DIABETIC NEUROPATHY/

A genetic predisposition to develop a polyneuropathy in case of diabet es seems to exist. Some ethnic groups such as North Africans are prone to develop a diabetic polyneuropathy. To identify this predisposition could help in targeting a preventive treatment. We have observed that red cell Na/K ATPase activity was lower among diabetic patients than controls and even fewer when diabetic neuropathy was present. Note an impaired NA/K ATPase activity has been implicated in the pathogenesis of diabetic neuropathy and ethnic differences in this enzyme activity have been demonstrated For these reasons, we have compared red cell Na /K ATPase activity of European and North African individuals with or w ithout diabetes and in case of diabetes with or without neuropathy. Am ong European subjects, Na/K ATPase activity was higher in 46 control s ubjects than in 84 insulin-dependent diabetic patients (405 +/- 16 nmo l.mg Prot-1h-I versus 282 +/- 10 p. < 0.05) and in the diabetic group Na/K ATPase activity was lower in the patients presenting with neuropa thy (242 +/- 19 versus 323 +/- 12 p. < 0.05). The mean red cell Na/K A TPase activity mts lower in 16 North African control subjects than in their European counterparts (296 +/- 26 p. < 0.05). The same observati on was made when comparing 24 North Africans insulin dependent diabeti c patients to the European diabetics (246 +/- 20 p. < 0.05). A low Na/ K ATPase activity appears to be a risk marker of diabetic neuropathy, it could explain the propensity of North African patients to develop t his diabetic complication. A restriction polymorphism exist on the fir st intron of the ATP1 A1 gene coding for the ATPase alpha I isoform. T his isoform is preponderent in the nervous tissue and exclusive in red cells. Among European diabetic individuals, the presence of the restr icted allele is strongly associated to diabetic neuropathy, confering a relative risk of 6.5 (95%, confidence interval 3.3-13). The restrict ed allele is associated to a lower Na/K ATPase activity but only among diabetic patients and not in control subjects. This fact suggests an interaction between genetic factors (the restriction polymorphism of A TP1 AI gene) and environmental factors (diabetes) to induce a decrease in Na/K ATPase activity which in turn could favor the development of diabetic neuropathy. Among North African individuals the impairment of Na/K ATPase activity is not explained by the presence of this polymor phism. Other genetic factors remain to be identified.