title: Variation in the CBP gene involved in epigenetic control associates with cognitive function.
abstract: Research into the pathologic mechanisms of neurodegenerative diseases has revealed that CREB binding protein (CBP) plays an important role in cognitive dysfunction. Loss of one copy of this gene leads to a syndrome with severe cognitive dysfunction. We investigated the association between four common variants in the CBP gene and cognitive function in 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Baseline associations between genetic variation and cognitive function were assessed with linear regression. Longitudinal associations were assessed with linear mixed models. All analyses were adjusted for sex, age, education, country, version of test, and pravastatin use. The intron 4CT and intron 3AC polymorphisms in the CBP gene were associated with better cognitive performance at baseline and during follow-up. Furthermore, the haplotype with the variant alleles of these two polymorphisms also showed a protective effect on cognitive function in all cognitive domains (all p<0.03). Genetic variation in the CBP gene is associated with better cognitive performance in an elderly population. Future research is necessary to investigate the effect of these polymorphisms on the expression of CBP levels and how these polymorphisms affect the gene expression mediated by CBP.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands. s.trompet@lumc.nl
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: D
authors.initials: D
authors.lastname: Pons
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: D
authors.initials: D
authors.lastname: Kremer
authors.forename: Eduard L E M
authors.initials: EL
authors.lastname: Bollen
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050882:CREB-Binding Protein / Q000235:genetics*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D057890:Epigenomics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017035:Pravastatin / Q000627:therapeutic use; D014652:Vascular Diseases / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050882:CREB-Binding Protein; D017035:Pravastatin