Candidate gene association study of insulin signaling genes and Alzheimer's disease: Evidence for SOS2, PCK1, and PPARγ as susceptibility loci
Hamilton G., Proitsi P., Jehu L., Morgan A., Williams J., O'Donovan MC., Owen MJ., Powell JF., Lovestone S.
Epidemiological evidence supports the existence of a possible link between type II diabetes mellitus (T2DM) and late-onset Alzheimer's disease (LOAD). Polymorphisms from candidate genes for T2DM were genotyped in a two-stage approach to identify novel risk factors for LOAD. One hundred fifty-two polymorphisms were initially genotyped in a case:control cohort: nine SNPs showed individual association with disease status under at least one genetic model, while an additional two SNPs showed a haplotype association. In a replication study, we confirmed significant association of SNPs within three genes - PPARγ, SOS2, and PCK1 - with Alzheimer's disease. In particular, our data suggest that the effect of variants within these genes might be influenced by gender. © 2007 Wiley-Liss, Inc.