Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two-year follow up study

Authors

  • Brenda Yan Fu,

    Corresponding author
    1. Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
    • Department of Psychiatry, a/f Multi-Centre, Tai Po Hospital, Tai Po, NT, Hong Kong SAR, China.
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  • Suk Ling Ma,

    1. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
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  • Nelson Leung Sang Tang,

    1. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
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  • Cindy Woon Chi Tam,

    1. Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Victor Wing Cheong Lui,

    1. Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Helen Fung Kum Chiu,

    1. Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China
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  • Linda Chiu Wa Lam

    1. Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China
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Abstract

Objectives

We previously found that the polymorphisms of cholesterol 24-hydroxylase (CYP46A1) gene were associated with the risk of Alzheimer's disease (AD) in Chinese. However, its effect in predicting progression of cognitive decline remains unknown.

Methods

Two hundred and eighty-one Chinese subjects (121 cognitively intact, 101 with mild cognitive impairment and 59 with mildly dementia) were followed-up with a mean (SD) duration of 25.22(5.74) months. Association between the CYP46A1 gene polymorphisms and 2-year cognitive deterioration were evaluated.

Results

At follow-up, 225(80.0%) subjects were reassessed. Sixty-three subjects were diagnosed as AD, 68 were MCI and 94 were cognitively intact. Among them, 158 had improved or remained stable while 67 deteriorated. The ‘deteriorated’ group was older than ‘improved or stable’ group (t-test, t = −2.87, p < 0.001). IVS2-150 polymorphism was associated with a higher risk of cognitive deterioration. Subjects with T allele were more likely to deteriorate compared with those without T allele (Pearson χ2 = 8.98, df 2, p= 0.011). IVS3-128 CC genotype was higher in ‘improved or stable’ group (Likelihood Ratio = 6.55, df 2, p= 0.038), suggesting a protective role for this allele. The two other polymorphisms, IVS1-192 and IVS4-122, did not show any significant association with cognitive function.

Conclusion

CYP46A1 gene may act to modulate the course of cognitive deterioration in late life. Copyright © 2009 John Wiley & Sons, Ltd.

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