Absence of association between intronic polymorphism in PS-1 gene and alzheimer's disease in italian patients

A genetic association between an intronic polymorphism in the PS-1 gene and late onset AD was recently reported. Homozigosity of the PS-1 gene allele 7 was associated with a significantly increased risk for late-onset Alzheimer's disease. This finding was then replicated by at least two independent groups but was not confirmed in a large series of late onset AD patients. We have studied the presence of this intronic polymorphism located 3' of exon 9 of PS-1 gene in 93 Italian sporadic AD patients (40 males, 53 females, 62 with age-atonset > 65 years and 31 with age-at-onset < 65) who met the NINCDS-ADRDA criteria for probable AD and in 60 normal controls. DNA samples were also genotyped for Apolipoprotein-E (ApoE) polymorphism. No significant excess of the 1/1 genotype in late onset probable AD patients nor in early-onset patients was detected. Allele frequency was comparable in all groups examined. In addition, there was no significant interaction between ApoE and PS-1 genotypes. Our results do not confirm previous studies, suggesting that PS-1 intronic polymorphism is not a susceptibility factor for AD in Italian patients. Finally, our data suggest that the ApoE-e4 associated Alzheimer's disease risk is not modified by PS-1 gene alleles.