The Effects of Two Polymorphisms on @entity994 Function and Their Association with XXXX in a Population of European Descent.

@entity1 @entity8 @entity2204 @entity5 @entity303 @entity191 @entity179 @entity195 @entity994
UNASSIGNED: With the exception of @entity2204 , genome-wide association studies have failed to identify strong genetic risk factors for late-onset @entity195 , despite strong evidence of heritability, suggesting that many low penetrance genes may be involved. Additionally, the nature of the identified genetic risk factors and their relation to disease pathology is also largely obscure. Previous studies have found that a @entity5 -associated variant of the cell cycle inhibitor gene @entity994 is associated with increased risk of @entity195 . The aim of this study was to confirm this association and to elucidate the effects of the variant on protein function and Alzheimer-type pathology. We examined the association of the @entity994 variant with @entity195 and @entity191 with @entity303 . The genotyping studies were performed on 719 @entity1 of the Oxford Project to Investigate Memory and Ageing, 225 @entity1 of a @entity191 DNA bank, and 477 @entity1 of the @entity1 Random Control collection available from the European Collection of Cell Cultures. The post mortem studies were carried out on 190 @entity1 . In the in-vitro study, @entity1 @entity8 were transfected with either the common or rare @entity994 variant; and cytometry was used to assess cell cycle kinetics, @entity994 protein expression and sub-cellular localisation. The variant was associated with an increased risk of @entity195 , and @entity191 with @entity303 , relative to age matched controls. Furthermore, the variant was associated with an earlier age of onset of @entity195 , and a more severe phenotype, with a primary influence on the accumulation of tangle pathology. In the in-vitro study, we found that the SNPs reduced the cell cycle inhibitory and anti-apoptotic activity of @entity994 . The results suggest that the @entity5 -associated variant of @entity994 may contribute to the loss of cell cycle control in neurons that may lead to @entity179 .
