A study of the association between the ADAM 12 and SH3PXD2A (SH3MD1) genes and Alzheimer's disease

Several observations suggest that neurotoxicity in Alzheimer's disease (AD) can be partly attributed to beta-amyloid (A beta) and senile plaques. Recent work has suggested that the FISH (five SH3 domains) adapter protein and ADAM12 (a disintegrin and metalloprotease) may mediate the neurotoxic effect of A beta. Both genes are located on chromosome 10, within a region linked to AD (for SH3PXD2A) or nearby (for ADAM12). A recent study reported a statistically significant interaction between 2 variants of these genes (rs3740473 for SH3PXD2A and rs11244787 for ADAM12) with respect to the risk of developing AD. With a view to replicating this observation, we genotyped the two SNPs in four European case-control cohorts of Caucasian origin (1913 cases and 1468 controls) but were unable to confirm the initial results. (C) 2009 Elsevier Ireland Ltd. All rights reserved.