title: Mutation screening and association study of the neprilysin gene in sporadic Alzheimer's disease in Chinese persons.
abstract: Neprilysin has been reported to be a major beta-amyloid peptide (Abeta)-degrading enzyme. The decreased expression and activity of it may contribute to the development of Alzheimer's disease by promoting the accumulation of Abeta. We used denaturing high-performance liquid chromatography to screen the neprilysin gene (NEP) for single nucleotide polymorphisms (SNPs) in 257 Chinese sporadic Alzheimer's disease patients and 242 cognitive normal controls. As a result, eight novel and one known SNP were identified. Three of them, -204G-->C in the promoter region, IVS17-294C-->T, and IVS22+36C-->A showed a significant association with Alzheimer's disease (p = .006,.017, and.003, respectively). Subsequent haplotype analysis provided further evidence of the association (global p < .0001 for the three SNPs mentioned above, and global p < .01 for the eight SNPs with rare allele frequency > 1%). These findings indicate that genetic variations within or extremely close to NEP might influence the susceptibility to Alzheimer's disease in Chinese persons.
authors.affiliation: Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Shi
authors.forename: Sizhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Mouni
authors.initials: M
authors.lastname: Tang
authors.forename: Cui
authors.initials: C
authors.lastname: Ma
authors.forename: Jinghua
authors.initials: J
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Xiehe
authors.initials: X
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yangbo
authors.initials: Y
authors.lastname: Guo
authors.forename: Haiying
authors.initials: H
authors.lastname: Han
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D001483:Base Sequence; D002681:China / Q000453:epidemiology; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015260:Neprilysin / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011336:Probability; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015260:Neprilysin