Sheng-Yuan Liu1,2, He-Dan Zhao3, Jin-Long Wang3, Tong Huang4, Hua-Wei Tian5, Li-Fen Yao6, Hua Tao1, Zhong-Wei Chen2, Chang-Yi Wang2, Si-Tong Sheng7, Hua Li8, Bin Zhao9, Ke-Shen Li1. 1. Key Laboratory of Aging-related cardio-cerebral Diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China. 2. Department of Chronic Noncommunicable Disease Control, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China. 3. Department of Clinical Psychology, The Kangci Hospital, Jiaxing, China. 4. Community Health Service Center of Nanyou, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, China. 5. Department of Prevention and Health, The Futian People's Hospital, Shenzhen, China. 6. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China. 7. College of Life Sciences, Shenzhen University, Shenzhen, China. 8. HYK High-throughput Biotechnology Institute, Shenzhen, China. 9. Institute of Neurology, Guangdong Medical College, Zhanjiang, China.
Abstract
AIMS: 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). CONCLUSION: 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.
AIMS: 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 ADpatients 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 AKT1rs2498786 polymorphism. The CC frequency of AKT1rs2498786 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 AKT1rs2498786 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). CONCLUSION: The study suggests that AKT1rs2498786 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 ADpatients with T2D.
Authors: Suzanne Craft; Sanjay Asthana; David G Cook; Laura D Baker; Monique Cherrier; Kristina Purganan; Colby Wait; Andreana Petrova; Shawn Latendresse; G Stennis Watson; John W Newcomer; Gerard D Schellenberg; Aaron J Krohn Journal: Psychoneuroendocrinology Date: 2003-08 Impact factor: 4.905
Authors: Jean-Vianney Haure-Mirande; Mickael Audrain; Tomas Fanutza; Soong Ho Kim; William L Klein; Charles Glabe; Ben Readhead; Joel T Dudley; Robert D Blitzer; Minghui Wang; Bin Zhang; Eric E Schadt; Sam Gandy; Michelle E Ehrlich Journal: Acta Neuropathol Date: 2017-06-13 Impact factor: 17.088