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

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.

• Authors: 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
• Journal: Experimental gerontology (Exp Gerontol) Vol. 44 Issue 5 Pg. 350-5 (May 2009) ISSN: 1873-6815 [Electronic] England
• PMID: 19249341 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Validation Study)

Chemical References

• Interleukin-6
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases

Topics

• Aged
• Aged, 80 and over
• Aging (genetics)
• Cardiovascular Diseases (blood, genetics, mortality)
• Case-Control Studies
• Female
• Genetic Variation
• Genotype
• Humans
• Inflammation (blood, genetics, mortality)
• Interleukin-6 (blood, genetics)
• Longevity (genetics)
• Male
• Phenotype
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases (blood, genetics)
• Risk Factors