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).