title: Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease.
abstract: Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.
authors.affiliation: Kasaoka Hospital, Kasaoka, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takehisa
authors.forename: Takaki
authors.initials: T
authors.lastname: Imamura
authors.forename: Naohiko
authors.initials: N
authors.lastname: Uchida
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kanzaki
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Okumura
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D015260:Neprilysin / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D012333:RNA, Messenger; D004247:DNA; D015260:Neprilysin