title: Contribution of the Akt2 gene to type 2 diabetes in the Chinese Han population.
abstract: BACKGROUND
  The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass. In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized by insulin resistance, and to further identify if variations in this gene have a relationship with type 2 diabetes, we sequenced the entire coding region and splice junctions of Akt2 and made a further case-control study to explore the association between 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 was within 25 to 45 years old. The body mass index of all the participants was lower than 28 kg/m(2) and all of them were insulin-resistant (the fasting insulin level > 100 pmol/L or 16 µIU/ml). The entire coding region and splice junctions of Akt2 were directly sequenced in these 23 probands. SNPs with a frequency of minor allele over 20 percent were selected to be further studied in a case-control study. We chose 743 non-diabetic subjects as the control group and 742 type 2 diabetic patients as the case group. All these subjects were genotyped. A Snapshot Technology Platform (Applied Biosystems) was used for genotyping.
  
  
  RESULTS
  The Akt2 genes from all 23 subjects were successfully sequenced. We did not identify any mutation in the type 2 diabetic pedigree. Two SNPs were identified, 13010323T > C and 13007939G > T. 13010323T > C was in intron 9, which was the location of rs2304188 reported in Genbank. Its minor allele frequency was 13.04%. 13007939G > T was in the 3'-untranslated region (UTR) of exon 14, which was the location of rs2304186 reported in Genbank. Its minor allele frequency was 34.78%. The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported in Genbank. In the case-control study with 742 patients and 743 controls, there was no significant difference between the two 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 by insulin resistance. There is no significant relationship between rs2304186 and type 2 diabetes in the Chinese Han population.
authors.affiliation: Department of Endocrinology and Metabolism, Peking University Diabetes Center, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Xiu-Qin
authors.initials: XQ
authors.lastname: Sun
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Luo
authors.forename: Ling-Wang
authors.initials: LW
authors.lastname: An
authors.forename: Lin
authors.initials: L
authors.lastname: Chu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Huo
authors.forename: Xue-Yao
authors.initials: XY
authors.lastname: Han
authors.forename: Xiang-Hai
authors.initials: XH
authors.lastname: Zhou
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Li-Nong
authors.initials: LN
authors.lastname: Ji
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
chemical_list: C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt