[Genetic factors, Na K ATPase activity and neuropathy in diabetics]

A genetic predisposition to develop a polyneuropathy in case of diabetes 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 lower when diabetic neuropathy was present. Now 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 without diabetes and in case of diabetes with or without neuropathy. Among European subjects, Na/K ATPase activity was higher in 46 control subjects than in 84 insulin-dependent diabetic patients (405 +/- 16 nmol.mg Prot-1h-1 versus 282 +/- 10 p. < 0.05) and in the diabetic group Na/K ATPase activity was lower in the patients presenting with neuropathy (242 +/- 19 versus 323 +/- 12 p. < 0.05). The mean red cell Na/K ATPase activity was lower in 16 North African control subjects than in their European counterparts (296 +/- 26 p. < 0.05). The same observation was made when comparing 24 North Africans insulin dependent diabetic 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 this diabetic complication. A restriction polymorphism exist on the first intron of the ATP1 A1 gene coding for the ATPase alpha 1 isoform. This isoform is preponderent in the nervous tissue and exclusive in red cells. Among European diabetic individuals, the presence of the restricted allele is strongly associated to diabetic neuropathy, confering a relative risk of 6.5 (95%, confidence interval 3.3-13). The restricted 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 ATP1 A1 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 impairement of Na/K ATPase activity is not explained by the presence of this polymorphism. Other genetic factors remain to be identified.