Journal article
An Interleukin-18 Polymorphism Is Associated With Reduced Serum Concentrations and Better Physical Functioning in Older People
The journals of gerontology. Series A, Biological sciences and medical sciences, Vol.62(1), pp.73-78
01/2007
DOI: 10.1093/gerona/62.1.73
PMCID: PMC2669299
PMID: 17301041
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.
Details
- Title: Subtitle
- An Interleukin-18 Polymorphism Is Associated With Reduced Serum Concentrations and Better Physical Functioning in Older People
- Creators
- Timothy M. Frayling - University of PlymouthSajjad Rafiq - University of PlymouthAnna Murray - University of PlymouthAlison J. Hurst - University of PlymouthMichael N. Weedon - University of PlymouthWilliam Henley - University of PlymouthStefania Bandinelli - National Research CouncilAnna-Maria Corsi - University of FlorenceLuigi Ferrucci - National Institutes of HealthJack M. Guralnik - National Institutes of HealthRobert B. Wallace - University of IowaDavid Melzer - University of Plymouth
- Resource Type
- Journal article
- Publication Details
- The journals of gerontology. Series A, Biological sciences and medical sciences, Vol.62(1), pp.73-78
- DOI
- 10.1093/gerona/62.1.73
- PMID
- 17301041
- PMCID
- PMC2669299
- NLM abbreviation
- J Gerontol A Biol Sci Med Sci
- ISSN
- 1079-5006
- eISSN
- 1758-535X
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 01/2007
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984364456002771
Metrics
22 Record Views