title: Association of HSP70 and its co-chaperones with Alzheimer's disease.
abstract: The heat shock protein (HSP) 70 family has been implicated in the pathology of Alzheimer's disease (AD). In this study, we examined common genetic variations in the 80 genes encoding HSP70 and its co-chaperones. We conducted a study in a series of 462 patients and 5238 unaffected participants derived from the Rotterdam Study, a population-based study including 7983 persons aged 55 years and older. We genotyped a total of 12,053 Single Nucleotide Polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. Replication was performed in two independent cohort studies, the Framingham Heart study (FHS; n = 806) and Cardiovascular Health Study (CHS; n = 2150). When adjusting for multiple testing, we found a small but consistent, though not significant effect of rs12118313 located 32 kb from PFDN2, with an OR of 1.19 (p-value from meta-analysis = 0.003). However this SNP was in the intron of another gene, suggesting it is unlikely this SNP reflects the effect of PFDN2. In a formal pathway analysis we found nominally significant evidence for an association of BAG, DNAJA and prefoldin with AD. These findings corroborate with those of a study of 2032 AD patients and 5328 controls, in which several members of the prefoldin family showed evidence for association to AD. Our study did not reveal evidence for a genetic variant if the HSP70 family with a major effect on AD. However, our findings of the single SNP analysis and pathway analysis suggest that multiple genetic variants in prefoldin are associated with AD.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Broer
authors.forename: Mohammad Arfan
authors.initials: MA
authors.lastname: Ikram
authors.forename: Maaike
authors.initials: M
authors.lastname: Schuur
authors.forename: Anita L
authors.initials: AL
authors.lastname: DeStefano
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.forename: William T
authors.initials: WT
authors.lastname: Longstreth
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Yurii
authors.initials: Y
authors.lastname: Aulchenko
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.forename: Annette L
authors.initials: AL
authors.lastname: Fitzpatrick
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones