title: Genetic variation in BIN1 gene and Alzheimer's disease risk in Han Chinese individuals.
abstract: Genome-wide association studies have identified the bridging integrator 1 (BIN1) gene as the most important genetic susceptibility locus in late-onset Alzheimer's disease (LOAD) after apolipoprotein E for individuals of European ancestry. To further characterize this association and to isolate the variants within BIN1 contributing to LOAD in Han Chinese individuals, we conducted a 2-step design study in our cohort of 1133 LOAD patients and 1159 control subjects. Sequencing analysis identified 44 variants within BIN1. Follow-up genotyping analysis revealed that a novel missense mutation P318L appeared to exert risk effect for development of LOAD; and rs67327804 was also significantly associated with LOAD risk even after adjusting for age, gender, and apolipoprotein E ε4 status. Haplotype analysis confirmed that the "GA" haplotype derived from single-nucleotide polymorphisms in rs67327804 and rs1060743 showed a 1.4-fold increased risk of LOAD. Our findings provided the first independent evidence that variants in BIN1 were significantly associated with LOAD in Han Chinese individuals.
authors.affiliation: School of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: School of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China; Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. Electronic address: yu-jintai@163.com.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: School of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
authors.forename: Hua-Shi
authors.initials: HS
authors.lastname: Guan
authors.affiliation: School of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China; Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. Electronic address: dr.tanlan@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins
keywords: Alzheimer's disease; Association study; Bridging integrator 1; Polymorphism; Susceptibility