TY - JOUR T1 - Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults. JF - Exp Gerontol Y1 - 2009 A1 - Walston, Jeremy D A1 - Matteini, Amy M A1 - Nievergelt, Caroline A1 - Lange, Leslie A A1 - Fallin, Dani M A1 - Barzilai, Nir A1 - Ziv, Elad A1 - Pawlikowska, Ludmila A1 - Kwok, Pui A1 - Cummings, Steve R A1 - Kooperberg, Charles A1 - LaCroix, Andrea A1 - Tracy, Russell P A1 - Atzmon, Gil A1 - Lange, Ethan M A1 - Reiner, Alex P KW - Aged KW - Aged, 80 and over KW - Aging KW - Cardiovascular Diseases KW - Case-Control Studies KW - Female KW - Genetic Variation KW - Genotype KW - Humans KW - Inflammation KW - Interleukin-6 KW - Longevity KW - Male KW - Phenotype KW - Poly (ADP-Ribose) Polymerase-1 KW - Poly(ADP-ribose) Polymerases KW - Risk Factors AB -

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.

VL - 44 IS - 5 U1 - https://www.ncbi.nlm.nih.gov/pubmed/19249341?dopt=Abstract ER -