Association of heat shock proteins with all-cause mortality
| Autor: | K. L. Lunetta, C.M. van Duijn, A.G. Uitterlinden, Stefania Bandinelli, Linda Broer, A. M. Arnold, Yongmei Liu, Marcus Dörr, Joanne M. Murabito, W. Hoffmann, Toshiko Tanaka, Thomas Kocher, Albert Hofman, Ellen W. Demerath, Albert V. Smith, Jerome I. Rotter, David Karasik, Bruce M. Psaty, Vilmundur Gudnason, Robert C. Kaplan, Ben A. Oostra, Kurt Lohman, Lenore J. Launer, G. J. Tranah, Luigi Ferrucci, S. Walter, H. Wallaschofski, M. E. Garcia, Nora Franceschini, Henning Tiemeier, Tamara B. Harris, Douglas P. Kiel, Gil Atzmon, G. Homuth, A.B. Newman |
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| Přispěvatelé: | Epidemiology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Clinical Genetics |
| Rok vydání: | 2012 |
| Předmět: |
Aging
Genotype Transcription Genetic Longevity Population Single-nucleotide polymorphism Biology Article 03 medical and health sciences Rotterdam Study 0302 clinical medicine Cause of Death Heat shock protein Humans Promoter Regions Genetic education Genotyping Heat-Shock Proteins Retrospective Studies 030304 developmental biology Aged 80 and over Genetics 0303 health sciences education.field_of_study Heat shock proteins General Medicine All-cause mortality United States 3. Good health Hsp70 Heat shock factor HEAT shock factor 2 Ageing Immunology Geriatrics and Gerontology 030217 neurology & neurosurgery Forecasting |
| Zdroj: | Age, 35(4), 1367-1376. Springer International Publishing AG Age |
| ISSN: | 1574-4647 0161-9152 |
| DOI: | 10.1007/s11357-012-9417-7 |
| Popis: | Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality. Electronic supplementary material The online version of this article (doi:10.1007/s11357-012-9417-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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