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Association of Single-Nucleotide Polymorphism in ANK1 with Late-Onset Alzheimer’s Disease in Han Chinese

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Abstract

Recently, two CpG sites in ankyrin 1 (ANK1) gene were identified to be hypermethylated and associated with Alzheimer’s disease (AD)-related neuropathology in two large independent studies. Genetic variations are indicated to be involved in DNA methylation, especially when the associated single-nucleotide polymorphisms (SNPs) are located adjacent to the CpG site. Accordingly, ANK1 polymorphisms might contribute to late-onset AD (LOAD) risk. One polymorphism rs515071 was identified to be a potential risk factor for type 2 diabetes (T2D). As shared genetic background was found underlying T2D and AD, we postulate that rs515071 polymorphism may be associated with late-onset AD (LOAD) risk and assessed the association in 982 LOAD patients and 1346 sex- and age-matched healthy controls. Our results showed that minor allele A of rs515071 significantly increased LOAD risk in the APOE ε4 (+) subgroup (genotype P = 0.015, allele P = 0.020). After adjusting for age and gender, the association remained significant under the dominant model (OR = 1.809, 95 % confidence interval (CI) = 1.186–2.757, P = 0.006). In conclusion, our findings demonstrate that rs515071 in ANK1 is a novel genetic risk for LOAD susceptibility in Han Chinese.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81471309, 81371406, 81171209, 81571245, 81501103), the Scientific Research Foundation for the Excellent Middle-Aged and Youth Scientists of Shandong Province (BS2013YY028), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

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Authors and Affiliations

  1. Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China

    Song Chi & Jing-Hui Song

  2. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao, Shandong Province, 266071, China

    Song Chi, Meng-Shan Tan, Zi-Xuan Wang, Lan Tan & Jin-Tai Yu

  3. Department of Emergency, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, People’s Republic of China

    Wei Zhang

  4. Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China

    Teng Jiang

  5. Memory and Aging Center, Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA, 94158, USA

    Jin-Tai Yu

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  1. Song Chi
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Correspondence to Lan Tan or Jin-Tai Yu.

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Song Chi and Jing-Hui Song are regarded as co-first authors.

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Chi, S., Song, JH., Tan, MS. et al. Association of Single-Nucleotide Polymorphism in ANK1 with Late-Onset Alzheimer’s Disease in Han Chinese. Mol Neurobiol 53, 6476–6481 (2016). https://doi.org/10.1007/s12035-015-9547-x

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  • DOI: https://doi.org/10.1007/s12035-015-9547-x

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