Objective: To investigate the association of the single nucleotide polymorphisms (SNPs) A-->G in the intron 2 of cholesterol 24-hydroxylase (CYP46) gene and G-->A (R219K) in the exon 6 of ATP-binding cassette transporter A1 (ABCA1) gene with sporadic Alzheimer's disease (SAD) in the Han Chinese population.
Methods: Peripheral blood samples were collected from 168 SAD patients, 74 males and 94 females, aged 74 +/- 8 (52 - 95), with an average age at onset of 69 +/- 7 (47 - 86), and sex-, and age-matched 215 healthy persons. PCR-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes. Apolipoprotein E (ApoE) genotyping was conducted. The strength of association between the polymorphisms and AD was estimate.
Results: The frequency of ApoE genotype of the SAD patients was 14%, significantly higher than that of the controls (5.1%, chi(2) = 19.060, P < 0.01). The risk of SAD in those with at least one epsilon 4 allele was 2.8 times that in those without epsilon 4 allele (OR = 2.82, 95% CI = 1.54 - 5.17, P = 0.001). There was no significant difference in the genotype or allele frequencies for CYP46 gene between the SAD patients and controls. However, there was an obvious association between the polymorphism of ABCA1 gene and SAD (chi(2) = 8.230, P = 0.016). The frequency of G/A + A/A genotypes in the SAD patients was 61.3%, significantly lower than that of the controls (73.5%, chi(2) = 6.444, P = 0.011). The risk of SAD in the carriers of A alleles (G/A + A/A genotypes) was significantly lower than those with GG genotype by 43% (adjusted OR = 0.57, 95% CI = 0.36 - 0.91, P = 0.019), and the risk of SAD in the AA homozygote carriers was significantly lower than that of the GG genotype carriers by 60% (adjusted OR = 0.40; 95% CI = 0.21 - 0.77, P = 0.006).
Conclusion: The CYP46 intron 2 polymorphism may not be associated with the risk of AD, but AA genotype or A allele of ABCA1 gene may have a protective effect for AD in Han Chinese.