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

TitleInflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.
Publication TypeJournal Article
Year of Publication2009
AuthorsWalston, JD, Matteini, AM, Nievergelt, C, Lange, LA, Fallin, DM, Barzilai, N, Ziv, E, Pawlikowska, L, Kwok, P, Cummings, SR, Kooperberg, C, LaCroix, A, Tracy, RP, Atzmon, G, Lange, EM, Reiner, AP
JournalExp Gerontol
Volume44
Issue5
Pagination350-5
Date Published2009 May
ISSN1873-6815
KeywordsAged, Aged, 80 and over, Aging, Cardiovascular Diseases, Case-Control Studies, Female, Genetic Variation, Genotype, Humans, Inflammation, Interleukin-6, Longevity, Male, Phenotype, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases, Risk Factors
Abstract<p>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.</p>
DOI10.1016/j.exger.2009.02.004
Alternate JournalExp Gerontol
PubMed ID19249341
PubMed Central IDPMC2791897
Grant ListR01 AG027236 / AG / NIA NIH HHS / United States
N01HV48195 / HL / NHLBI NIH HHS / United States
N01HG65403 / HG / NHGRI NIH HHS / United States
HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U19 AG023122 / AG / NIA NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R01 HL-071862 / HL / NHLBI NIH HHS / United States
P30 AG021334 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
R01 HL071862-04 / HL / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
R01 HL071862 / HL / NHLBI NIH HHS / United States
P01 AG027734 / AG / NIA NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
R01 HL077449 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 AG018728 / AG / NIA NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
U01 HL066682 / HL / NHLBI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States