Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: The cardiovascular health study

Alexander P. Reiner, Paula Diehr, Warren S. Browner, Stephen E. Humphries, Nancy S. Jenny, Mary Cushman, Russell P. Tracy, Jeremy Walston, Thomas Lumley, Anne B. Newman, Lewis H. Kuller, Bruce M. Psaty

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, β-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women ≥65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.

Original languageEnglish (US)
Pages (from-to)175-183
Number of pages9
JournalAtherosclerosis
Volume181
Issue number1
DOIs
StatePublished - Jul 1 2005

Keywords

  • Fibrinolysis
  • Inflammation
  • Longevity
  • Promoter polymorphism
  • Thrombin-activatable fibrinolysis inhibitor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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