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We have investigated the association of two candidate genes on chromosome 14, presenilin 1 (PS1) and alpha1-antichymotrypsin (ACT), with the risk of sporadic Alzheimer's disease (AD) by using 427 AD cases and 250 controls. The frequency of the ACT*A allele was significantly higher in cases than controls (0.550 vs 0.466). The stratification of the ACT data by PS1 genotypes showed that the risk associated with the ACT*A allele was confined to PS1*1 carriers only. The two-site haplotype data for PS1 and ACT showed that the A1 haplotype, carrying the ACT*A and PS1*1 alleles, was more frequent in cases than controls (0.310 vs 0.251), whereas the frequency of the T2 haplotype, carrying the ACT*T and PS1*2 alleles, was lower in cases than controls (0.177 vs 0.237). These data indicate a possible synergistic effect of these two loci on the risk of AD.
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