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Association of HSP70 and its co-chaperones with Alzheimer's disease.
Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
| Title | Association of HSP70 and its co-chaperones with Alzheimer's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Broer, L, Ikram, MArfan, Schuur, M, DeStefano, AL, Bis, JC, Liu, F, Rivadeneira, F, Uitterlinden, AG, Beiser, AS, Longstreth, WT, Hofman, A, Aulchenko, Y, Seshadri, S, Fitzpatrick, AL, Oostra, BA, Breteler, MMB, van Duijn, CM |
| Journal | J Alzheimers Dis |
| Volume | 25 |
| Issue | 1 |
| Pagination | 93-102 |
| Date Published | 2011 |
| ISSN | 1875-8908 |
| Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Cohort Studies, Genetic Association Studies, Genetic Variation, HSP70 Heat-Shock Proteins, Humans, Middle Aged, Molecular Chaperones, Polymorphism, Single Nucleotide |
| Abstract | <p>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.</p> |
| DOI | 10.3233/JAD-2011-101560 |
| Alternate Journal | J. Alzheimers Dis. |
| PubMed ID | 21403392 |
| PubMed Central ID | PMC3483142 |
| Grant List | N01-HC-25195 / HC / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States R01 NS017950 / NS / NINDS NIH HHS / United States AG15928 / AG / NIA NIH HHS / United States R01 AG015928-02 / AG / NIA NIH HHS / United States 02-HL-6-4278 / HL / NHLBI NIH HHS / United States R01 AG016495 / AG / NIA NIH HHS / United States U01 HL080295-04 / HL / NHLBI NIH HHS / United States R01 HL087652-03 / HL / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States R01 AG016495-10S1 / AG / NIA NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States P30 DK063491-03 / DK / NIDDK NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States M01 RR000425-36 / RR / NCRR NIH HHS / United States R01 AG008122-20 / AG / NIA NIH HHS / United States P30 AG013846-15 / AG / NIA NIH HHS / United States N02HL64278 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States P50 AG005133-23 / AG / NIA NIH HHS / United States R01 NS017950-29 / NS / NINDS NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States AG05133 / AG / NIA NIH HHS / United States M01RR00425 / RR / NCRR NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States N01 HC055222 / HC / NHLBI NIH HHS / United States P30AG013846 / AG / NIA NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States R01 AG020098-09 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States AG031287 / AG / NIA NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States R01 AG031287-02 / AG / NIA NIH HHS / United States R01 AG025259 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States AG16495 / AG / NIA NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States AG20098 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States AG025259 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R01 AG033193-03 / AG / NIA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R01 AG025259-05 / AG / NIA NIH HHS / United States R01 AG031287 / AG / NIA NIH HHS / United States |