title: Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.
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, beta-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 > or = 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.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA 98101, USA. apreiner@u.washington.edu
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.forename: Paula
authors.initials: P
authors.lastname: Diehr
authors.forename: Warren S
authors.initials: WS
authors.lastname: Browner
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
mesh_terms: D000368:Aged; D000375:Aging; D025901:Carboxypeptidase B2 / Q000235:genetics; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006304:Health Status; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D025901:Carboxypeptidase B2