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

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.