title: Association between Polymorphisms of the AKT1 Gene Promoter and Risk of the Alzheimer's Disease in a Chinese Han Population with Type 2 Diabetes.
abstract: OBJECTIVE
  Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with type 2 diabetes (T2D) where the v-akt murine thymoma viral oncogene homolog 1 (AKT1) plays an important role in the protein synthesis pathways and cell apoptosis processes. Evidence has been shown that AKT1 protein may be related to AD risk among patients with T2D. The aim of this study was to analyze the potential association between single nucleotide polymorphisms of AKT1 promoter and the risk of AD among patients with T2D.
  
  
  METHODS
  The association between AKT1 polymorphisms and AD risk in patients with T2D was assessed among 574 consecutive unrelated subjects including 112 AD patients with T2D, 231 patients with AD, and 231 healthy controls in a case-control study. The cognitive function of all subjects was assessed using MMSE. Six single nucleotide polymorphisms with minor allele frequency >0.2 (rs2498786, rs74090038, rs2494750, rs2494751, rs5811155, and rs2494752) in AKT1 promoter were analyzed by polymerase chain reaction (PCR), and the concentration of AKT1 protein in serum was tested using enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Overall, there was statistically significant difference in AKT1 rs2498786 polymorphism. The CC frequency of AKT1 rs2498786 polymorphism in AD with T2D group and AD control group was significantly higher than that in healthy control group (PAD+T2D vs. health < 0.0001, PAD vs. health < 0.0001). However, the difference was not found between AD with T2D group and AD control group. Compared with healthy control group, the plasma levels of AKT1 protein in AD with T2D group (PAD+T2D vs. health < 0.0001) and AD control group (PAD vs. health = 0.0003) decreased significantly. Among genotypes of AKT1 rs2498786 polymorphism, the AKT1 protein level in GG genotype was significantly higher than that in GC genotype (PGG vs. GC < 0.0001) and CC genotype (PGG vs. CC < 0.0001).
  
  
  CONCLUSIONS
  The study suggests that AKT1 rs2498786 polymorphism in insulin signaling pathway may be associated with AD risk and different genotypes may affects levels of protein expression. However, the polymorphism is not shown to be exclusive in AD patients with T2D.
authors.affiliation: Key Laboratory of Aging-related cardio-cerebral Diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.|Department of Chronic Noncommunicable Disease Control, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China.
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Clinical Psychology, The Kangci Hospital, Jiaxing, China.
authors.forename: He-Dan
authors.initials: HD
authors.lastname: Zhao
authors.affiliation: Department of Clinical Psychology, The Kangci Hospital, Jiaxing, China.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Community Health Service Center of Nanyou, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Prevention and Health, The Futian People's Hospital, Shenzhen, China.
authors.forename: Hua-Wei
authors.initials: HW
authors.lastname: Tian
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Yao
authors.affiliation: Key Laboratory of Aging-related cardio-cerebral Diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Chronic Noncommunicable Disease Control, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Department of Chronic Noncommunicable Disease Control, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Si-Tong
authors.initials: ST
authors.lastname: Sheng
authors.affiliation: HYK High-throughput Biotechnology Institute, Shenzhen, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Aging-related cardio-cerebral Diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors.forename: Ke-Shen
authors.initials: KS
authors.lastname: Li
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood / Q000235:genetics*; D012306:Risk
chemical_list: C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Alzheimer's disease; insulin signaling pathway; polymorphism; type 2 diabetes; v-akt murine thymoma viral oncogene homolog 1