Premium
Cholesterol 24‐hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two‐year follow up study
Author(s) -
Fu Brenda Yan,
Ma Suk Ling,
Tang Nelson Leung Sang,
Tam Cindy Woon Chi,
Lui Victor Wing Cheong,
Chiu Helen Fung Kum,
Lam Linda Chiu Wa
Publication year - 2009
Publication title -
international journal of geriatric psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 129
eISSN - 1099-1166
pISSN - 0885-6230
DOI - 10.1002/gps.2196
Subject(s) - allele , medicine , cognition , dementia , genotype , cognitive decline , clinical dementia rating , polymorphism (computer science) , alzheimer's disease , cognitive impairment , allele frequency , chinese people , disease , gastroenterology , psychology , genetics , biology , gene , psychiatry , china , law , political science
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 χ 2 = 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.