title: Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians.
abstract: Systemic low-grade inflammation is consistently associated with functional status, cognitive functioning, multimorbidity, and survival in oldest olds. If inflammation is either a cause or a consequence of age-related pathology, genetic determinants of late-life survival can reside in cytokine genes polymorphisms, regulating inflammatory responses. The aim of this study was to test associations between commonly studied polymorphisms in interleukin (IL)6, IL10, IL15, and IL18, and tumor necrosis factor-alpha genes and late-life survival in a longitudinal cohort of nonagenarians: the Danish 1905 cohort. Additionally, associations were investigated between inflammatory markers and major predictors of mortality as cognitive and functional status. Modest sex-specific associations were found with survival, cognitive functioning, and handgrip strength. Evaluation of combined genotypes indicated that, in nonagenarian men, the balance of pro- and anti-inflammatory activity at IL18 and IL10 loci is protective against cognitive decline. In conclusion, in this large study with virtually complete follow-up, commonly studied polymorphisms in cytokine genes do not have a major impact on late-life survival or associated risk phenotypes.
authors.affiliation: The Danish Aging Research Center, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 9, DK-5000 Odense, Denmark. s.dato@unical.it
authors.forename: Serena
authors.initials: S
authors.lastname: Dato
authors.forename: Karen S
authors.initials: KS
authors.lastname: Krabbe
authors.forename: Mikael
authors.initials: M
authors.lastname: Thinggaard
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Helle
authors.initials: H
authors.lastname: Bruunsgaard
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D002423:Cause of Death / Q000639:trends; D016207:Cytokines / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
chemical_list: D016207:Cytokines