title: Lack of association between the polymorphisms of beta-site APP-cleaving enzyme 2 (BACE2) 5'-flanking region and sporadic Alzheimer's disease.
abstract: Amyloid beta-peptide (A beta) plays a central role in the pathogenesis of Alzheimer's disease (AD). A beta is produced by sequential cleavage of the amyloid precursor protein (APP) by two enzymes referred to as beta- and gamma-secretase. beta-secretase is of more importance, as it catalyses the rate-limiting step in the production of A beta. Although beta-site APP-cleaving enzyme 1 (BACE1) is known to cleave APP at the beta-secretase site as required for the generation of A beta, the role of its homologue BACE2 is controversial. For seeking the correlation of the BACE2 promoter with sporadic AD (SAD), we performed a case-control study in a Chinese Han population. In the study, we sequenced the 2641 bp fragment of the 5'-flanking region of BACE2 gene and found three polymorphisms which are -320C/- (rs11316732), -1541A/T (rs9975138) and -1904C/T (rs28656880). Definitive genotyping these markers and apolipoprotein E (APOE) polymorphism were surveyed using restriction enzyme digestion and direct sequencing in 359 SAD patients and 334 controls. We failed to find any association between these three polymorphisms and SAD even after statistical adjustment for age, gender and APOE epsilon 4 status. Our data do not support that there is a linkage between the 5'-flanking region polymorphisms of BACE2 and SAD in the Chinese Han population.
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Key Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing 100053, PR China.
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Yu
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
mesh_terms: D024506:5' Flanking Region; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015183:Restriction Mapping; D012306:Risk; D017422:Sequence Analysis, DNA; D012737:Sex Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human