TY - JOUR
T1 - Interleukin-18 polymorphism and physical functioning in older people
T2 - A replication study and meta-analysis
AU - Thomas, Kate
AU - Rafiq, Sajjad
AU - Frayling, Timothy M.
AU - Ebrahim, Shah
AU - Kumari, Meena
AU - Gallacher, John
AU - Ferrucci, Luigi
AU - Bandinelli, Stefania
AU - Wallace, Robert B.
AU - Melzer, David
AU - Martin, Richard M.
AU - Ben-Shlomo, Yoav
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Ageing
KW - Gait speed
KW - IL-18
KW - Interleukin-18 polymorphism
KW - Physical function
KW - Walk time
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U2 - 10.1093/gerona/glp092
DO - 10.1093/gerona/glp092
M3 - Article
C2 - 19633236
AN - SCOPUS:70350454764
SN - 1079-5006
VL - 64
SP - 1177
EP - 1182
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 11
ER -