Interleukin-18 polymorphism and physical functioning in older people: A replication study and meta-analysis

Kate Thomas, Sajjad Rafiq, Timothy M. Frayling, Shah Ebrahim, Meena Kumari, John Gallacher, Luigi Ferrucci, Stefania Bandinelli, Robert B. Wallace, David Melzer, Richard M. Martin, Yoav Ben-Shlomo

Research output: Contribution to journalArticlepeer-review


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 Ore. We meta-analyzed (JV = 6,141) the results with data from the original paper reporting this association: IowaEstablished 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.

Original languageEnglish (US)
Pages (from-to)1177-1182
Number of pages6
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number11
StatePublished - 2009
Externally publishedYes


  • Ageing
  • Gait speed
  • IL-18
  • Interleukin-18 polymorphism
  • Physical function
  • Walk time

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

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