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

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

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)350-355
Number of pages6
JournalExperimental Gerontology
Volume44
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • Genetic epidemiology
  • IL-6
  • Inflammation
  • Longevity
  • PARP1

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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  • Cite this

    Walston, J. D., Matteini, A. M., Nievergelt, C., Lange, L. A., Fallin, D. M., Barzilai, N., Ziv, E., Pawlikowska, L., Kwok, P., Cummings, S. R., Kooperberg, C., LaCroix, A., Tracy, R. P., Atzmon, G., Lange, E. M., & Reiner, A. P. (2009). Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults. Experimental Gerontology, 44(5), 350-355. https://doi.org/10.1016/j.exger.2009.02.004