No association between a 3' untranslated region polymorphism in the neprilysin gene and Alzheimer's disease in the Japanese population

Abstract

Background: Alzheimer's disease (AD) is caused by neuronal cell death with aggregation of amyloid-β (Aβ) in the brain cortex and hippocampus. Neprilysin (NEP) plays an important role mainly in the degradation of Aβ. The NEP-knockout mouse shows low degradation of Aβ and is confirmed to have AD. The frequency of the C/C genotype of NEP159 C/T polymorphism in the 3' untranslated region (UTR) of the NEP gene Apolipoprotein E (Apo E) ε4 group has been reported to be higher than that of the control group. In the present study, we screened for the polymorphism in our Japanese AD and control subjects. Furthermore, we searched for a new polymorphism in exon 1 and exon 24 in the NEP gene. Methods: 121 sporadic AD (SAD) patients were recruited from among the inpatients and outpatients of the hospital the authors work in. The 101 age-matched control subjects were recruited from healthy volunteers with no history of dementia or other neuropsychiatrie diseases. The NEP159 C/T polymorphism and Apo E were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and a new polymorphism was detected by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method. Results: We confirmed that the frequency of the Apo E ε4-allele was higher in the SAD group than in the control group. There was no significant difference in genotypic distribution of the NEP159 C/T polymorphism between the control and SAD groups. Conclusion: Our studies suggest that there is no genetic association between the NEP159 C/T polymorphism and the risk of Japanese SAD. Our results indicate that further genetic studies of the NEP gene should be performed in other ethnic groups.