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Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.
Tuesday,2012-11-06 12:10 America/Los_Angeles — eenright
| Title | Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Walston, 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 |
| Journal | Exp Gerontol |
| Volume | 44 |
| Issue | 5 |
| Pagination | 350-5 |
| Date Published | 2009 May |
| ISSN | 1873-6815 |
| Keywords | Aged, 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> |
| DOI | 10.1016/j.exger.2009.02.004 |
| Alternate Journal | Exp Gerontol |
| PubMed ID | 19249341 |
| PubMed Central ID | PMC2791897 |
| Grant List | R01 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 |