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Genetic Association Between APP, ADAM10 Gene Polymorphism, and Sporadic Alzheimer’s Disease in the Chinese Population

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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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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81200987; No.81470058; No.81401055) and the Natural Science Foundation Project of CQCSTC (Grant No. CSTC2010BB5029). The authors would like to thank Shanghai Genesky Bio-Tech Genetic Core Lab for assistance in genotyping techniques.

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology and Center for Clinical Neuroscience, Daping Hospital and Institute of Field Surgery, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, China

    Fan Zeng, Cheng Shen, Yu-Hui Liu, Jing Li, Jie Zhu, Ye-Ran Wang, Jia-Chuan Yan, Chang-Yue Gao, Hua-Dong Zhou, Juan Deng & Yan-Jiang Wang

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  1. Fan Zeng
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  2. Cheng Shen
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Correspondence to Juan Deng or Yan-Jiang Wang.

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Zeng, F., Shen, C., Liu, YH. et al. Genetic Association Between APP, ADAM10 Gene Polymorphism, and Sporadic Alzheimer’s Disease in the Chinese Population. Neurotox Res 27, 284–291 (2015). https://doi.org/10.1007/s12640-015-9516-1

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