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) Ε4-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 ApoEΕ4 was confirmed to be a genetic risk factor for AD (p = 0.0016, OR = 2.76, 95% CI = 1.50–5.11).