Contribution of the Akt2 gene to type 2 diabetes in the Chinese Han population

Background The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process.Akt2 issuggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and isletmass.In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized byinsulin resistance,and to further identify if variations in this gene have a relationship with type 2 diabetes,we sequencedthe entire coding region and splice junctions of Akt2 and made a further case-control study to explore the associationbetween single-nucleotide polymorphisms(SNPs)in this gene and type 2 diabetes in the Chinese Han population.Methods We selected 23 probands with a type 2 diabetic pedigree whose family members’ average onset age waswithin 25 to 45 years old.The body mass index of all the participants was lower than 28 kg/m~2 and all of them wereinsulin-resistant(the fasting insulin level>100 μmol/L or 16 μlU/ml).The entire coding region and splice junctions of Akt2were directly sequenced in these 23 probands.SNPs with a frequency of minor allele over 20 percent were selected tobe further studied in a case-control study.We chose 743 non-diabetic subjects as the control group and 742 type 2diabetic patients as the case group.All these subjects were genotyped.A Snapshot Technology Platform(AppliedBiosystems)was used for genotyping.Results The Akt2 genes from all 23 subjects were successfully sequenced.We did not identify any mutation in the type2 diabetic pedigree.Two SNPs were identified,13010323T>C and 13007939G>T.13010323T>C was in intron 9,whichwas the location of rs2304188 reported in Genbank.Its minor allele frequency was 13.04%.13007939G>T was in the3’-untranslated region(UTR)of exon 14,which was the location of rs2304186 reported in Genbank.Its minor allelefrequency was 34.78%.The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported inGenbank.In the case-control study with 742 patients and 743 controls,there was no significant difference between thetwo groups for the allele frequency of rs2304186(odd ratio:0.96,95% confidence interval:0.82-1.12,P=0.597).Conclusions The Akt2 gene is not a major cause of diabetes in a non-obese Chinese Han population characterized byinsulin resistance.There is no significant relationship between rs2304186 and type 2 diabetes in the Chinese Han population.