title: Interleukin-18 polymorphism and physical functioning in older people: a replication study and meta-analysis.
abstract: 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.
authors.affiliation: Department of Social Medicine, University of Bristol, Bristol BS8 2PS, UK. kate.thomas@bristol.ac.uk
authors.forename: Kate
authors.initials: K
authors.lastname: Thomas
authors.forename: Sajjad
authors.initials: S
authors.lastname: Rafiq
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: John
authors.initials: J
authors.lastname: Gallacher
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wallace
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D016138:Walking
chemical_list: D020382:Interleukin-18