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1 Department of Medical Genetics
2 Institute of Mental Health, West China Hospital, Sichuan University, Chengdu, China.
3 Division of Human Morbid Genomics, State Key Laboratory of Biotherapy of Human Diseases, Chengdu, China.
4 Guangzhou Psychiatric Hospital, Guangzhou Medical College, Guangzhou, China.
5 International Center for Health and Society, Department of Epidemiology and Public Health, London, United Kingdom.
6 Department of Psychological Medicine, Institute of Psychiatry, London, United Kingdom.
Address correspondence to Professor Sizhong Zhang, Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu, 610041, China. E-mail: szzhang{at}mcwcums.com
Neprilysin has been reported to be a major beta-amyloid peptide (Aß)-degrading enzyme. The decreased expression and activity of it may contribute to the development of Alzheimer's disease by promoting the accumulation of Aß. 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, 204GC in the promoter region, IVS17294C
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.
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