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Open Access Publications from the University of California

Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.

  • Author(s): Walston, Jeremy D
  • Matteini, Amy M
  • Nievergelt, Caroline
  • Lange, Leslie A
  • Fallin, Dani M
  • Barzilai, Nir
  • Ziv, Elad
  • Pawlikowska, Ludmila
  • Kwok, Pui
  • Cummings, Steve R
  • Kooperberg, Charles
  • LaCroix, Andrea
  • Tracy, Russell P
  • Atzmon, Gil
  • Lange, Ethan M
  • Reiner, Alex P
  • et al.

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Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15%-20% higher baseline IL-6 concentration per copy among CHS European-American (EA) participants (all p<10(-4)). In a case/control analysis nested within this EA cohort, the minor allele of PARP1 rs1805415 was nominally associated with decreased longevity (p=0.001), but there was no evidence of association between IL6R genotype and longevity. The PARP1 rs1805415--longevity association was subsequently replicated in one of two independent case/control studies. In a pooled analysis of all three studies, the "risk" of longevity associated with the minor allele of PARP1 rs1805415 was 0.79 (95%CI 0.62-1.02; p=0.07). These findings warrant further study of the potential role of PARP1 genotype in inflammatory and aging-related phenotypes.

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