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CYP46A1 T/C polymorphism associated with the APOEε4 allele increases the risk of Alzheimer’s disease

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Abstract

Studies of the relationship between Alzheimer’s disease (AD) and single nucleotide polymorphism (SNP) T/C in intron 2 of the cholesterol-24S-hydroxylase gene (CYP46A1) have reported inconsistent results. To confirm the association between the CYP46A1 T/C polymorphism and AD risk, a meta-analysis containing 4,875 AD cases and 4,874 controls from 21 case–control studies was performed. There were 16 studies involving Europeans, four studies with Asians and one study with Africans. The combined results of overall analysis showed that the CYP46A1 T/C polymorphism increased the risk of AD significantly in recessive model [CC versus CT + TT, odds ratio (OR) = 1.20, 95 % confidence interval (CI) = 1.04–1.38, p = 0.01]. On subgroup analysis by ethnicity, similarly significant differences in recessive model were also found in Europeans. Another analysis of the synergistic effect of the CYP46A1 T/C polymorphism and the ε4 allele of the apolipoprotein E gene (APOE ε4) was performed in eight studies with available stratified information. The results revealed that the presence of APOE ε4 allele could strengthen the effect of CC genotype on AD risk, and the reverse was also true. In conclusion, our meta-analysis has successfully proved that CC genotype of the CYP46A1 T/C polymorphism could increase the risk of AD, and this effect would be weakened in APOE ε4 non-carriers and strengthened in APOE ε4 carriers.

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Conflicts of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. Six authors of this paper are willing to provide their autographs if necessary.

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All human studies must state that they have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, No. 10 Changjiang Branch Road, Daping, Chongqing, 400042, China

    Ling Li, Zegang Yin, Juan Liu, Gongbo Li, Yanjiang Wang, Jiachuan Yan & Huadong Zhou

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  1. Ling Li
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  2. Zegang Yin
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  3. Juan Liu
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  4. Gongbo Li
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  7. Huadong Zhou
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Correspondence to Huadong Zhou.

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Li, L., Yin, Z., Liu, J. et al. CYP46A1 T/C polymorphism associated with the APOEε4 allele increases the risk of Alzheimer’s disease. J Neurol 260, 1701–1708 (2013). https://doi.org/10.1007/s00415-012-6690-4

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  • DOI: https://doi.org/10.1007/s00415-012-6690-4

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