The Relationship Between Na/K ATPase Activity And ATP1A1 Gene Polymorphism And Diabetic Neuropathy

Diabetic neuropathy is one of the diabetic complications and a significant source of disability in elderly diabetic patients,but the mechanism of diabetic neuropathy has not been completely known.A lot of researches suggest that decrease of Na/K ATPase activity plays a role in the development of diabetic neuropathy. Na/K ATPase is encoded by various genes,of which the gene ATP1A1 is expressed predominantly in peripheral nerves and erythrocytes.Many factors affect the activity of Na/K ATPase in red blood cells,which is different in different ethnic.Diabetes mellitus induces a decrease in Na/K ATPase activity in man and animals and gene mutation augments the decrease,which leads to appearance of diabetic neuropathy.We measure the activity of Na/K ATPase and examine the gene ATP1A1 in type 2 diabetes mellitus by PCR-RFLP to investigate the relationship between Na/K ATPase activity and ATP1A1 gene polymorphism and diabetic neuropathy.MethodsWe divide the patients into three groups:1)diabetes mellitus with diabetic neuropathy;2) diabetes mellitus without diabetic neuropathy;3)control group with normal fast blood glucose and without diabetes mellitus family history.We measure the activity of Na/K ATPase by chemical method and amplify the gene ATP1A1 then digest the second exon of the ATP1A1 by the PstI restriction enzyme. ResultsThe analysis revealed Na/K ATPase activity is significantly lower in type 2 diabetes mellitus patients with neuropathy than that of control group and T2DM patients without neuropathy. T2DM patients with neuropathy were significantly different from T2DM patients without neuropathy in genotype distribution(χ2=11.085,p<0.05).Morbidity of diabetic neuropathy in the patients with restrictive allele A is 66.3% and morbidity of the noncarriers is 85%,OR=2.883,95%CI=1.337~6.217,p<0.05.In conclusion the allele A is the protective factor of diabetic neuropathy.In T2DM Na/K ATPase activity in the patients who carry the restrictive allele A is different from that of noncarriers(4.64±3.03nmolPi/107RBC/h vs3.13±1.24nmolPi/107RBC/h).ConclusionsATP1A1 gene polymorphism is associated with Na/K ATPase activity and diabetic neuropathy in type 2 diabetes mellitus. Na/K ATPase activity of diabetes mellitus patients with diabetic neuropathy is significantly lower than that of diabetes mellitus patients without neuropathy.The risk in type 2 diabetes mellitus patients with restrictive allele A to accompany with diabetic neuropathy is distinctively higher than noncarriers.