Adenylate kinase locus 1 genetic polymorphism and type 2 diabetes

Abstract

AK1 catalyzes the reversible reaction ATP+AMP ? 2ADP thus contributing to the regulation of relative concentration of these important nu-cleotides. Intracellular ATP is a storage of en-ergy for cellular processes, moreover extracel-lular ATP together with ADP, AMP and adeno-sine are critical signalling molecule for sending messages to nearby cells acting on P1 and P2 receptors. AK1 shows a genetic polymorphism and recently our group has shown that the cor-relation between blood glucose and glycated haemoglobin in T2D is dependent on AK1 phe-notype. In the present paper we have carried further studies on the relationship between AK1 phenotypes and T2D. Possible interactions with ABO blood groups and ACP1 polymorphism have also been investigated. We have re-ex-amined the data on 280 subjects with type 2 diabetes from the White population of Penne (Central Italy). 384 consecutive healthy new-borns from the same population have been also studied. A three way contingency table analysis was carried out according to Sokal and Rohlf and other statistical analyses by SPSS pro-grams. T2D patients with AK12-1 phenotype have higher values of blood glucose level and glycated haemoglobin and an increased ten-dency to dyslipidemia and retinopathy. In addi-tion there is an interaction of AK1 with ABO blood groups and with ACP1 polymorphism. The different activity between AK1 phenotypes could influence the relative concentration of ATP, ADP, AMP and adenosine with important effects on metabolic activity thus explaining the associa-tion of AK1 with clinical manifestation of T2D.