Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients.
BACKGROUND
Cholesterol metabolism has been implicated in the pathophysiology of Alzheimer's disease (AD), and cholesterol-related genes are plausible candidate genes for AD. Genetic association of CYP46A1 polymorphisms with AD had been under extensive investigations; however, observations on intron 2 T-->C (rs754203) generated inconclusive results.


OBJECTIVE
To analyse an independent data set in a Chinese population to see whether the polymorphic site rs754203 of the CYP46A1 gene is associated with AD.


METHODS
We analysed 130 sporadic AD patients and 110 healthy controls of the Southern Chinese origin.


RESULTS
An association between the genotype frequency and AD was suggested in the general population (p = 0.047, odds ratio, OR = 1. 61, 95% confidence interval, CI = 0.96-2.70), while the association was most significant in the apolipoprotein E (ApoE) epsilon4-negative group (p = 0.004, OR = 2.54, 95% CI =1.31-4.95). Linkage disequilibrium block prediction results also favoured this association. Consistent with previous reports, intron 3 C-->T (rs4900442) polymorphism did not show any evidence of association; in our data set ApoEepsilon4 was confirmed to be a genetic risk factor for AD (p = 0.0016, OR = 2.76, 95% CI = 1.50-5.11).
Li
Y
Y
Department of Biochemistry, University of Hong Kong, Hong Kong, SAR, China.
Chu
L W
LW
Chen
Y Q
YQ
Cheung
B M Y
BM
Leung
R Y H
RY
Yik
P Y
PY
Ng
K M
KM
Mak
W
W
Jin
D Y
DY
St George-Hyslop
P
P
Song
Y Q
YQ
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D000072556:Cholesterol 24-Hydroxylase; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
D053327:Apolipoprotein E4; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase