Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians

Systemic low-grade infl ammation is consistently associated with functional status, cognitive functioning, multimorbidity,and survival in oldest olds. If infl ammation is either a cause or a consequence of age-related pathology, genetic determinantsof late-life survival can reside in cytokine genes polymorphisms, regulating infl ammatory responses. The aim ofthis study was to test associations between commonly studied polymorphisms in interleukin (IL)6, IL10, IL15, and IL18,and tumor necrosis factor- a genes and late-life survival in a longitudinal cohort of nonagenarians: the Danish 1905cohort. Additionally, associations were investigated between infl ammatory markers and major predictors of mortality ascognitive and functional status. Modest sex-specifi c associations were found with survival, cognitive functioning, andhandgrip strength. Evaluation of combined genotypes indicated that, in nonagenarian men, the balance of pro- andanti-infl ammatory activity at IL18 and IL10 loci is protective against cognitive decline. In conclusion, in this largestudy with virtually complete follow-up, commonly studied polymorphisms in cytokine genes do not have a majorimpact on late-life survival or associated risk phenotypes.