Association of heat shock proteins with all-cause mortality.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Broer, L; Demerath, EW; Garcia, ME; Homuth, G; Kaplan, RC; Lunetta, KL; Tanaka, T; Tranah, GJ; Walter, S; Arnold, AM; Atzmon, G; Harris, TB; Hoffmann, W; Karasik, D; Kiel, DP; Kocher, T; Launer, LJ; Lohman, KK; Rotter, JI; Tiemeier, H; Uitterlinden, AG; Wallaschofski, H; Bandinelli, S; Dörr, M; Ferrucci, L; Franceschini, N; Gudnason, V; Hofman, A; Liu, Y; Murabito, JM; Newman, AB; Oostra, BA; Psaty, BM; Smith, AV; van Duijn, CM

Published Date

  • August 2013

Published In

Volume / Issue

  • 35 / 4

Start / End Page

  • 1367 - 1376

PubMed ID

  • 22555621

Pubmed Central ID

  • 22555621

Electronic International Standard Serial Number (EISSN)

  • 1574-4647

Digital Object Identifier (DOI)

  • 10.1007/s11357-012-9417-7

Language

  • eng

Conference Location

  • Netherlands