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


CONCLUSIONS
CYP46A1 gene may act to modulate the course of cognitive deterioration in late life.
Fu
Brenda Yan
BY
Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China. fuyan_1111@163.com
Ma
Suk Ling
SL
Tang
Nelson Leung Sang
NL
Tam
Cindy Woon Chi
CW
Lui
Victor Wing Cheong
VW
Chiu
Helen Fung Kum
HF
Lam
Linda Chiu Wa
LC
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002681:China; D000072556:Cholesterol 24-Hydroxylase; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism
D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase