%0 Journal Article %J Exp Gerontol %D 2009 %T Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults. %A Walston, Jeremy D %A Matteini, Amy M %A Nievergelt, Caroline %A Lange, Leslie A %A Fallin, Dani M %A Barzilai, Nir %A Ziv, Elad %A Pawlikowska, Ludmila %A Kwok, Pui %A Cummings, Steve R %A Kooperberg, Charles %A LaCroix, Andrea %A Tracy, Russell P %A Atzmon, Gil %A Lange, Ethan M %A Reiner, Alex P %K Aged %K Aged, 80 and over %K Aging %K Cardiovascular Diseases %K Case-Control Studies %K Female %K Genetic Variation %K Genotype %K Humans %K Inflammation %K Interleukin-6 %K Longevity %K Male %K Phenotype %K Poly (ADP-Ribose) Polymerase-1 %K Poly(ADP-ribose) Polymerases %K Risk Factors %X

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.

%B Exp Gerontol %V 44 %P 350-5 %8 2009 May %G eng %N 5 %1 https://www.ncbi.nlm.nih.gov/pubmed/19249341?dopt=Abstract %R 10.1016/j.exger.2009.02.004