TY - JOUR
T1 - Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults
T2 - The cardiovascular health study
AU - Reiner, Alexander P.
AU - Diehr, Paula
AU - Browner, Warren S.
AU - Humphries, Stephen E.
AU - Jenny, Nancy S.
AU - Cushman, Mary
AU - Tracy, Russell P.
AU - Walston, Jeremy
AU - Lumley, Thomas
AU - Newman, Anne B.
AU - Kuller, Lewis H.
AU - Psaty, Bruce M.
PY - 2005/7/1
Y1 - 2005/7/1
N2 - 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.
AB - 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.
KW - Fibrinolysis
KW - Inflammation
KW - Longevity
KW - Promoter polymorphism
KW - Thrombin-activatable fibrinolysis inhibitor
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U2 - 10.1016/j.atherosclerosis.2005.01.028
DO - 10.1016/j.atherosclerosis.2005.01.028
M3 - Article
C2 - 15939070
AN - SCOPUS:20444395843
VL - 181
SP - 175
EP - 183
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 1
ER -