Mutation screening and association study of the neprilysin gene in sporadic Alzheimer's disease in Chinese persons

Neprilysin has been reported to be a major beta-amyloid peptide (A beta)-degrading enzyme. The decreased expression and activity of it may contribute to the development of Alzheimer's disease by promoting the accumulation of A beta. 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.