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An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people.

ABSTRACT: 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.

SUBMITTER: Frayling TM

PROVIDER: S-EPMC2669299 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people.

Frayling Timothy M TM Rafiq Sajjad S Murray Anna A Hurst Alison J AJ Weedon Michael N MN Henley William W Bandinelli Stefania S Corsi Anna-Maria AM Ferrucci Luigi L Guralnik Jack M JM Wallace Robert B RB Melzer David D

The journals of gerontology. Series A, Biological sciences and medical sciences 20070101 1

<h4>Background</h4>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.<h4>Methods</h4>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 poly ...[more]

PMID: 17301041

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Project description:Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals that have long half-lives. Humans are exposed to PCBs and PBDEs mainly through diet, and relative to other populations, those who consume sport-caught fish generally have elevated body burdens. Numerous studies have found associations between prenatal exposure to these chemicals and neurodevelopmental deficits, but there are few studies assessing the impact of exposure during adolescence, a period of rapid development of executive functions. We assessed executive functions in adolescents at risk for exposure to PCBs and PBDEs through consumption of fish from the Lower Fox River and other contaminated waters in northeastern Wisconsin. Between 2007 and 2012, a sample of 115 12-18-year-old children was recruited from households in the Green Bay, WI area in which at least one parent held a WI fishing license. We assessed associations of total PCBs and total PBDEs, as well as the predominant individual congeners (PBDE 47 and 153; PCB 138/163, 153 and 180) with performance on four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intradimensional/Extradimensional Set-Shifting (ID/ED) which assesses cognitive flexibility, Delayed Matching to Sample (DMS) which assesses visual recognition memory, Spatial Working Memory (SWM), and Stockings of Cambridge (SOC) which assess planning and working memory. In addition to the exposure and outcome variables, multivariable regression models included the child's age, sex and IQ score as well as a sex by exposure interaction term. All of the children were non-Hispanic whites and most parents were married, employed, and had at least some college. After adjusting for serum lipids, the GM (GSD) for total PCBs (ng/g) was 30.83 (2.46), and the GM (GSD) for the predominant PCB congeners PCB 138/163, PCB 153, and PCB 180 were 4.60 (2.39), 5.43 (2.37), and 1.01 (2.71), respectively. The GM (GSD) for total PBDEs (ng/g) was 26.82 (3.30), and the GM (GSD) for the predominant PBDE congeners PBDE 47 and PBDE 153 were 16.64 (2.94) and 3.95 (3.43), respectively. For both chemicals, the primary finding of the negative binomial regression analyses was that higher blood serum concentrations were associated with poorer cognitive flexibility as measured on the ID/ED task. In particular, the PCB x sex interaction p-value was 0.08, and stratifying by sex demonstrated that males with higher blood serum total PCB concentrations (β = 2.20, 95% CL: 1.16, 4.16, p = 0.02) took more trials to complete the ID/ED task, while both males and females with higher total PBDE concentrations (β = 1.74, 95% CL: 1.25, 2.42, p = 0.001) took more total trials to complete the task. Higher serum total PCB concentrations were also associated with more errors on the DMS task (β = 1.15, 95% CL: 1.00, 1.31, p < 0.05). These findings suggest that exposure to PCBs or PBDEs during adolescence may be associated with impaired cognitive flexibility and that adolescent PCB exposure may be associated with visual recognition memory deficits.

Project description:BackgroundMedically unexplained physical symptoms (MUPS) are a leading cause of reduced work functioning. It is not known which factors are associated with reduced work functioning in people with moderate MUPS. Insight in these factors can contribute to prevention of reduced work functioning, associated work-related costs and in MUPS becoming chronic. Therefore, the aim of this study was to identify which demographic and health-related factors are associated with reduced work functioning, operationalized as impaired work performance and absenteeism, in people with moderate MUPS.MethodsData of 104 participants from an ongoing study on people with moderate MUPS were used in this cross-sectional study. Ten independent variables were measured at baseline to determine their association with reduced work functioning: severity of psychosocial symptoms (four domains, measured with the Four-Dimensional Symptom Questionnaire), physical health (RAND 36-Item Health Survey), moderate or vigorous physical activity (Activ8 activity monitor), age, sex, education level and duration of complaints. Two separate multivariable linear regression analyses were performed with backward stepwise selection, for both impaired work performance and absenteeism.ResultsAbsenteeism rate rose with 2.5 and 0.6% for every increased point on the Four-Dimensional Symptom Questionnaire for domain 'depression' (B = 0.025, SE = 0.009, p = .006) and domain 'somatization' (B = 0.006, SE = 0.003, p = .086), respectively. An R2 value of 0.118 was found. Impaired work performance rate rose with 0.2 and 0.5% for every increased point on the Four-Dimensional Symptom Questionnaire for domain 'distress' (B = 0.002, SE = 0.001, p = .084) and domain 'somatization' (B = 0.005, SE = 0.001, p < .001), respectively. An R2 value of 0.252 was found.ConclusionsSeverity of distress, probability of a depressive disorder and probability of somatization are positively associated with higher rates of reduced work functioning in people with moderate MUPS. To prevent long-term absenteeism and highly impaired work performance severity of psychosocial symptoms seem to play a significant role. However, because of the low percentage of explained variance, additional research is necessary to gain insight in other factors that might explain the variance in reduced work functioning even better.

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An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people.

Publications

An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people.

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