Recent studies have demonstrated that cholesterol metabolism might play an important role in Alzheimer's disease (AD). Cholesterol 24-hydroxylase (CYP46) and ATP-binding cassette transporter A1 (ABCA1) have both been proposed to be involved in cholesterol metabolism in the brain. The purpose of this case-control study was to determine whether single nucleotide polymorphisms (SNPs) A -> G in the intron 2 of CYP46 gene and G -> A (R219K) in the exon 7 of ABCA1 gene are associated with sporadic AD in the Chinese Han population. Genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) in 168 sporadic AD patients and 215 controls. There was no significant difference in the genotype or allele frequencies for CYP46 gene between AD patients and controls. However, we found an obvious association between the polymorphism of ABCA1 gene and AD (chi(2) =8.230, P=0.016). The risk for AD was significantly decreased in K allele (RK+KK genotypes) (adjusted OR=0.57, 95% CI=0.36-0.91, P=0.019) or KK homozygote carriers (adjusted OR=0.40; 95% CI=0.21-0.77, P=0.006) compared with RR genotypes carriers. Our results do not support a genetic association between the intron 2 polymorphism of CYP46 gene and the risk of sporadic AD, but reveal that KK genotype or K allele of ABCA1 gene may have a protective effect for sporadic AD in Chinese. (c) 2007 Elsevier B.V. All rights reserved.