期刊
EXPERIMENTAL GERONTOLOGY
卷 44, 期 5, 页码 350-355出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2009.02.004
关键词
Inflammation; IL-6; PARP1; Longevity; Genetic epidemiology
资金
- National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-55222, N01-HC-15103, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 AG027236, R01 HL-071862, R01 HL077449, R01 AG027734, N01-HC-85085, N01-HC-85083, N01-HC-85082, N01-HC-85081, N01-HC-85080, N01-HC-85084, N01-HV-48195]
- National Institute on Aging Longevity Consortium [U19 AG023122]
- National Institute on Aging Claude D. Pepper Older Americans Independence Centers [P30 AG021334]
- National Institute of neurological Disorders and Stroke
- Paul beeson Physician Faculty Scholar in Aging Award
- Ellison Medical Foundation Senior Scholar Award
- National Institutes of Health [R01 AG-18728OIAI, UOI HL66682, N01-HG-65403]
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. (C) 2009 Elsevier Inc. All rights reserved.
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