Apolipoprotein E and alpha-1-antichymotrypsin allele polymorphism in sporadic and familial Alzheimer's disease

Alzheimer disease (AD) patients with both sporadic and familial forms of AD and non-demented controls were genotyped for common polymorphisms in the s ignal peptide for ol-l-antichymotrypsin (ACT) gene and in two different reg ions of apolipoprotein E (APOE) gene. The ACT TT genotype was over-represen ted (P = 0.025) in patients with early onset of sporadic AD. In this patien t's group ACT TT genotype conferred a significant crude odds ratio for the disease (OR = 2.09; 95% CI = 1.09-4.00, P = 0.025). After adjustment for th e APOE epsilon 4 and APOE -491 genotypes, logistic regression analysis conf irmed that the ACT TT genotype resulted independently associated with early onset AD (adjusted OR = 2.56; 85% C.I. = 1.3-5.2, P = 0.009). The frequenc y of APOE epsilon 4 allele was increased in AD, as expected (OR = 5.92, 95% CI = 3.60-9.70, P = 0.0001). On the contrary, the APOE -491 A/T genotypes were not associated with AD. No preferential association of the APOE epsilo n 4 allele or APOE -491 A/T genotypes with ACT A/T alleles was observed in AD. Present findings indicated that subjects with ACT TT genotype had an in creased risk of developing AD and suggested that this genotype influenced t he risk of an early onset of the disease by affecting the production of ACT molecules. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.