apoe genotype-function relationship evidence of ？491 at promoter polymorphism modifying transcription control but not type 2 diabetes riskapoe genotype-function关系的证据 491年启动子多态性修改转录控制而不是2型糖尿病的风险.pdf

APOE Genotype-Function Relationship: Evidence of 2491 A/T Promoter Polymorphism Modifying Transcription Control but Not Type 2 Diabetes Risk 1¤ 1 2 1 1 1 1 Hua Geng , Peggy P. Y. Law , Maggie C. Y. Ng , Ting Li , Li-Yun Liang , Tian-Fang Ge , Kam-Bo Wong , 3 2 2 2 1,4 Chun Liang , Ronald C. Ma , Wing-Yee So , Juliana C. N. Chan , Yuan-Yuan Ho * 1 Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China, 2 Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China, 3 Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, China, 4 Genetics of Complex Disorder Program, Departments of Biostatistics and Psychiatry, Columbia University, New York, New York, United States of America Abstract Background: The apolipoprotein E gene (APOE) coding polymorphism modifies the risks of Alzheimer’s disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP) of the APOE promoter has also been shown to modify the risk of Alzheimer’s disease. Methodology/Principal Findings: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.e., in transcription control of the gene and in the risk of type 2 diabetes. In molecular studies, the effect of the APOE 2491A/T (rs449647) polymorphism on gene transcription was accessed by