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  • Title: Genetic association between APP, ADAM10 gene polymorphism, and sporadic Alzheimer's disease in the Chinese population.
    Author: Zeng F, Shen C, Liu YH, Li J, Zhu J, Wang YR, Yan JC, Gao CY, Zhou HD, Deng J, Wang YJ.
    Journal: Neurotox Res; 2015 Apr; 27(3):284-91. PubMed ID: 25631235.
    Abstract:
    Amyloid precursor protein (APP) is cleaved by β-secretase and γ-secretase complex, and subsequently generates amyloid-β peptide (Aβ). The Aβ cascade is widely accepted as playing a role in the pathogenesis Alzheimer's disease (AD). Meanwhile, procession of APP by α-secretase (mainly a disintegrin and metalloproteinase 10, ADAM10) precludes Aβ production, and produces soluble APP-α which is considered to be neuroprotective against AD. To explore the relationship between APP, ADAM10 gene polymorphism and sporadic AD (sAD), we conducted a case-control study in a Chinese Han cohort including 200 sAD patients and 243 control participants. Four target single nucleotide polymorphisms (SNPs) in or near the promoter of the APP gene and two in the promoter of the ADAM10 gene were selected and genotyped with a polymerase chain reaction-ligase detection reaction method. After adjustments for age, sex, and APOE ε4 status, only one target SNP, rs463946 was associated with the risk of sAD in the dominant (OR 1.52, 95 % CI 1.01-2.29, P = 0.045) and overdominant models (OR 1.59, 95 % CI 1.04-2.43, P = 0.031); the results also showed a borderline association of rs364048 (OR 1.53, 95 % CI 1.00-2.34, P = 0.048) and rs466433 (OR 1.53, 95 % CI 1.00-2.34, P = 0.048) with the risk of sAD in the overdominant model. However, these associations did not remain after multiple comparison correction. As for the ADAM10 gene, the two target SNPs (rs514049 and rs653765) were not associated with the risk of sAD either. No significant association was found between different haplotypes of the two genes and the risk of sAD. Conclusively, we did not find the association between APP, ADAM10 gene polymorphism, and the risk of sAD in our cohort of Chinese Han people.
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