Polymorphism of CYP46A1 Gene and Alzheimer’s Disease in the Iranian Population

Abstract

Background: Cholesterol homeostasis in the brain has been demonstrated in the pathogenesis of Alzheimer’s disease (AD). Experimental data support that brain cholesterol turnover can modulate central processes in AD pathogenesis. Excess cholesterol is eliminated from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46A1), a main mechanism of maintaining cholesterol homeostasis. The CYP46A1 gene has been suggested as a genetic risk factor for AD. Methods: In this case-control study, we analyzed an intronic CYP46A1 gene single-nucleotide polymorphism (SNP) in 100 AD patients and 80 age- and sex-matched control subjects in the Iranian population. Results: We found a significant difference in CYP46A1 TT-homozygotes genotype (χ2 = 5.06, df =1, P = 0.02) and T allele frequency (χ2 = 6.09, df = 1, P = 0.01) between AD patients and controls. Conclusions: The results of our study indicate that intron T/C polymorphism of the CYP46A1 gene is associated with AD in the Iranian population, and that the CYP46A1 TT genotype or T allele frequency might be a genetic risk factor for AD and increase susceptibility to AD.