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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.

SUBMITTER: Thomas K

PROVIDER: S-EPMC2981454 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Thomas Kate K Rafiq Sajjad S Frayling Timothy M TM Ebrahim Shah S Kumari Meena M Gallacher John J Ferrucci Luigi L Bandinelli Stefania S Wallace Robert B RB Melzer David D Martin Richard M RM Ben-Shlomo Yoav Y

The journals of gerontology. Series A, Biological sciences and medical sciences 20090724 11

<h4>Background</h4>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.<h4>Methods</h4>We examined the associatio ...[more]

PMID: 19633236

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Project description:BACKGROUND:The proinflammatory cytokine interleukin-18 (IL-18) is associated with major disabling conditions, although whether as byproduct or driver is unclear. The role of common variation in the IL-18 gene on serum concentrations and functioning in old age is unknown. METHODS:We used 1671 participants aged 65-80 years from two studies: the InCHIANTI study and wave 6 of the Iowa-Established Populations for Epidemiological Study of the Elderly (EPESE). We tested three common polymorphisms against IL-18 concentration and measures of functioning. RESULTS:In the InCHIANTI study, a 1 standard deviation increase in serum IL-18 concentrations was associated with an increased chance of being in the 20% of slowest walkers (odds ratio 1.45; 95% confidence interval, 1.17-1.80; p =.0007) and 20% of those with poorest function based on the Short Physical Performance Battery Score (odds ratio 1.52; 95% confidence interval, 1.22-1.89; p =.00016) in age sex adjusted logistic regression models. There was no association with Activities of Daily Living (p =.26) or Mini-Mental State Examination score (p =.66). The C allele of the IL-18 polymorphism rs5744256 reduced serum concentrations of IL-18 by 39 pmol/mL per allele (p =.00001). The rs5744256 single nucleotide polymorphism was also associated with shorter walk times in InCHIANTI (n = 662, p =.016) and Iowa-EPESE (n = 995, p =.026). In pooled ranked models rs5744256 was also associated with higher SPPB scores (n = 1671, p =.019). Instead of adjusting for confounders in the IL-18 walk time association, we used rs5744256 in a Mendelian randomization analysis: The association remained in instrumental variable models (p =.021). CONCLUSION:IL-18 concentrations are associated with physical function in 65- to 80-year-olds. A polymorphism in the IL-18 gene alters IL-18 concentrations and is associated with an improvement in walk speed. IL-18 may play an active role in age-related functional impairment, but these findings need independent replication.

Project description:ObjectivePreclinical and observational data suggest that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may be able to improve physical performance in older people via direct and indirect effects on skeletal muscle. We aimed to summarize current evidence from randomised controlled trials in this area.DesignSystematic review and meta-analysis.Setting and participantsRandomized controlled trials enrolling older people, comparing ACEi or ARB to placebo, usual care or another antihypertensive agent, with outcome data on measures of physical performance.MethodsWe searched multiple electronic databases without language restriction between inception and the end of February 2020. Trials were excluded if the mean age of participants was <65 years or treatment was targeting specific diseases known to affect muscle function (for example heart failure). Data were sought on measures of endurance and strength. Standardized mean difference (SMD) treatment effects were calculated using random-effects models with RevMan software.ResultsEight trials (952 participants) were included. Six trials tested ACEi, 2 trials tested ARBs. The mean age of participants ranged from 66 to 79 years, and the duration of treatment ranged from 2 months to 1 year. Trials recruited healthy older people and people with functional impairment; no trials specifically targeted older people with sarcopenia. Risk of bias for all trials was low to moderate. No significant effect was seen on endurance outcomes [6 trials, SMD 0.04 (95% CI -0.22 to 0.29); P = .77; I2 = 53%], strength outcomes [6 trials, SMD -0.02 (95% CI -0.18 to 0.14), P = .83, I2 = 21%] or the short physical performance battery [3 trials, SMD -0.04 (95% CI -0.19 to 0.11), P = .60, I2 = 0%]. No evidence of publication bias was evident on inspection of funnel plots.Conclusions and implicationsExisting evidence does not support the use of ACE inhibitors or angiotensin receptor blockers as a single intervention to improve physical performance in older people.

Project description:Introduction:The objectives of this review paper were to synthesize the data from randomized controlled trials in the literature to come to a conclusion on the effects of e-health interventions on promoting physical activity in older people. Methods:The Medline, CINAHL, Embase, PsycINFO, and SportDiscus databases were searched for articles about studies that 1) recruited subjects with a mean age of >?50?years, 2) tested e-health interventions, 3) employed control groups with no or less advanced e-health strategies, 4) measured physical activity as an outcome, 5) were published between 1st January 2008 and 31st May 2019, and 6) employed randomized controlled trials. The risk of bias in individual studies was assessed using the Physiotherapy Evidence Database scale. To examine the effects of the interventions, variables quantifying the amount of physical activity were extracted. The within-group effects of individual studies were summarized using Hedges g and 95% confidence intervals. Between-group effects were summarized by meta-analyses using RevMan 5.0 with a random effect model. Results:Of the 2810 identified studies, 38 were eligible, 25 were included in the meta-analyses. The within-group effect sizes (Hedges g) of physical activity in the intervention group at T1 ranged from small to large: physical activity time (0.12 to 0.84), step counts (-?0.01 to 11.19), energy expenditure (-?0.05 to 0.86), walking time (0.13 to 3.33), and sedentary time (-?0.12 to -?0.28). The delayed effects as observed in T2 and T3 also ranged from small to large: physical activity time (0.24 to 1.24) and energy expenditure (0.15 to 1.32). In the meta-analysis, the between-group effect of the e-health intervention on physical activity time measured by questionnaires, physical activity time measured by objective wearable devices, energy expenditure, and step counts were all significant with minimal heterogeneity. Conclusion:E-health interventions are effective at increasing the time spent on physical activity, energy expenditure in physical activity, and the number of walking steps. It is recommended that e-health interventions be included in guidelines to enhance physical activity in older people. Further studies should be conducted to determine the most effective e-health strategies.

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

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

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