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The CLU Gene rs11136000 Variant is Significantly Associated with Alzheimer’s Disease in Caucasian and Asian Populations

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Abstract

Large-scale genomewide association studies have reported that the CLU rs11136000 polymorphism is significantly associated with Alzheimer’s disease (AD) in people of Caucasian ancestry. Recently, this association was investigated in Asian populations (Chinese, Japanese, and Korean). However, these studies reported either a weak association or no association between the rs11136000 polymorphism and AD. We believe that this discrepancy may be caused by the relatively small sample size of the previous studies and the genetic heterogeneity of the rs11136000 polymorphism in AD among different populations. For this study, we searched the PubMed and AlzGene databases. We selected 18 independent studies (6 studies of Asian populations and 12 of populations of Caucasian ancestry) that evaluated the association between the rs11136000 polymorphism and AD using a case–control experimental design. We evaluated the genetic heterogeneity of the rs11136000 polymorphism in Caucasian and Asian populations. We then investigated the rs11136000 polymorphism by a meta-analysis in Asian populations using allele, dominant, and recessive models. We identified a significant association between rs11136000 and AD with the allele model (P = 2.00 × 10−4) and the dominant model (P = 5.00 × 10−3). Meanwhile, a similar genetic risk of the rs11136000 polymorphism in AD was observed in Asian and Caucasian populations. Further meta-analysis in pooled Asian and Caucasian populations indicated a more significant association with the allele (P = 8.30 × 10−24), dominant (P = 4.46 × 10−17), and recessive (P = 3.92 × 10−12) models. Collectively, our findings from this meta-analysis indicate that the effect of the CLU rs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.

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Acknowledgments

This research is supported by the grants from the National Nature Science Foundation of China (Grant Number 31171219, 81271213, and 31200934) and US–China Biomedical Collaborative Research Program (NSFC Grant Number 812111108) to Keshen Li.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute of Neurology, Guangdong Medical College, Zhanjiang, 524001, China

    Guiyou Liu, Guoda Ma, Bin Zhao & Keshen Li

  2. Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Beijing, China

    Guiyou Liu

  3. Department of Vascular Surgery of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China

    Haiyang Wang, Jingbo Li & Hali Li

  4. Department of Neurology, The First Hospital of Harbin, 151 Diduan Street, Daoli Region, Harbin, Heilongjiang, China

    Jiafeng Liu

  5. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

    Yongshuai Jiang

  6. Department of Human Genetics, University of California at Los Angeles, Los Angeles, CA, USA

    Zugen Chen

  7. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 524001, China

    Bin Zhao

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  1. Guiyou Liu
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  2. Haiyang Wang
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  3. Jiafeng Liu
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  5. Hali Li
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  6. Guoda Ma
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  7. Yongshuai Jiang
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  9. Bin Zhao
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  10. Keshen Li
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Correspondence to Haiyang Wang or Keshen Li.

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Guiyou Liu, Haiyang Wang, and Jiafeng Liu have contributed equally to this work.

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Liu, G., Wang, H., Liu, J. et al. The CLU Gene rs11136000 Variant is Significantly Associated with Alzheimer’s Disease in Caucasian and Asian Populations. Neuromol Med 16, 52–60 (2014). https://doi.org/10.1007/s12017-013-8250-1

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  • DOI: https://doi.org/10.1007/s12017-013-8250-1

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