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

Publication Type:

Journal Article

Source:

Experimental gerontology, Volume 44, Issue 5, p.350-5 (2009)

Keywords:

2009, Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Case-Control Studies, Center-Authored Paper, Female, Genetic Variation, Genotype, Humans, INFLAMMATION, Interleukin-6, Longevity, Male, PHENOTYPE, Poly(ADP-ribose) Polymerases, Public Health Sciences Division, Risk Factors

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.