BACKGROUND: Levels of the
proinflammatory cytokine interleukin-18 (IL-18) are raised in
old age and are associated with reduced physical functioning. Previous studies have indicated that the C
allele of the rs5744256 polymorphism in the IL-18 gene is strongly associated with reduced circulating IL-18 levels. This variant has previously been associated with improved locomotor performance in
old age, but the finding requires independent replication. METHODS: We examined the association between the IL-18 polymorphism rs5744256 and physical functioning in three cohorts with a total of 4,107 participants
aged 60-85 years: the English
Longitudinal Study of
Ageing, Caerphilly, and Boyd Orr. We meta-analyzed (N = 6,141) the results with data from the original paper reporting this association: Iowa-Established Populations for
Epidemiological Study of the
Elderly and InCHIANTI cohorts. Physical functioning was assessed by timed walks or the get up and go test. As locomotor performance tests differed between the cohorts and the distributions of times to complete the test (in seconds) were positively
skewed, we used the reciprocal transformation and computed study-specific z scores. RESULTS: Based on the three new studies, the estimated
linear regression coefficient per C
allele was 0.011 (95%
confidence interval [95% CI]: -0.04 to 0.06). A
meta-analysis that pooled the data from all studies showed weak evidence of an effect, with a
regression coefficient of 0.047 (95% CI: 0.010 to 0.083). CONCLUSIONS: We did not replicate an association between the IL-18 rs5744256 polymorphism and the physical function in people
aged 60-85 years. However, pooling data from all studies suggested a weak association of the C
allele of the rs5744256
single nucleotide polymorphism on improving walking times in
old age.