Polymorphisms in neprilysin gene affect the risk of Alzheimer’s disease in Finnish patients

Objectives: Neprilysin (NEP) is an amyloid β-peptide (Aβ) degrading enzyme expressed in the brain, and accumulation of Aβ is the neuropathological hallmark in Alzheimer’s disease (AD). In this study we investigated whether polymorphisms in the NEP gene have an effect on the risk for AD. Methods: The frequencies of seven single nucleotide polymorphisms (SNPs) and apolipoprotein E (APOE) were assessed in 390 AD patients and 468 cognitively healthy controls. Genotypes of the study groups were compared using binary logistic regression analysis. Haplotype frequencies of the SNPs were estimated from genotype data. Results: Two SNPs, rs989692 and rs3736187, had significantly different allelic and genotypic frequencies (uncorrected p = 0.01) between the AD and the control subjects and haplotype analysis showed significant association between AD and NEP polymorphisms. Conclusion: Taken together, these findings suggest that polymorphisms in the NEP gene increase risk for AD and support a potential role for NEP in AD.

[1]  Malcolm C Pike,et al.  A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort. , 2003, Human molecular genetics.

[2]  Jaume Bertranpetit,et al.  Possible increased risk for Alzheimer's disease associated with neprilysin gene , 2003, Journal of Neural Transmission.

[3]  M. Yamada,et al.  Lack of association of neprilysin polymorphism with Alzheimer's disease and Alzheimer's disease-type neuropathological changes , 2001, Journal of neurology, neurosurgery, and psychiatry.

[4]  H. Soininen,et al.  Genome-wide linkage disequilibrium mapping of late onset Alzheimer's disease in Finland , 2000, Neurobiology of Aging.

[5]  F. Rousset,et al.  AN EXACT TEST FOR POPULATION DIFFERENTIATION , 1995, Evolution; international journal of organic evolution.

[6]  M. Oda,et al.  Dinucleotide repeat polymorphisms in the Neprilysin gene are not associated with sporadic Alzheimer's disease , 2002, Neuroscience Letters.

[7]  D. Morello,et al.  Characterization of the 5' region of the CD10/neutral endopeptidase 24.11 gene. , 1995, Biochemical and biophysical research communications.

[8]  P. Mcgeer,et al.  Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of β-amyloid peptide , 2001, Neuroscience Letters.

[9]  T. Saido,et al.  Metabolic Regulation of Brain Aβ by Neprilysin , 2001, Science.

[10]  H. Soininen,et al.  Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease , 1996, Neurology.

[11]  B. Winblad,et al.  No association between polymorphisms in the neprilysin promoter region and Swedish Alzheimer's disease patients , 2003, Neuroscience Letters.