Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:301-306 (2005)
© 2005 The Gerontological Society of America

Mutation Screening and Association Study of the Neprilysin Gene in Sporadic Alzheimer's Disease in Chinese Persons

Jiajun Shi1,3,4, Sizhong Zhang1,3,, Mouni Tang4, Cui Ma4, Jinghua Zhao5, Tao Li2,6, Xiehe Liu2, Yan Sun1,3, Yangbo Guo4, Haiying Han4, Yongxin Ma1,3 and Zhenhuan Zhao4

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, –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.






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