Abstract
BackgroundAsthma is an increasingly common chronic disease among children, and data point toward a complex mechanism involving genetic, environmental and epigenetic factors. Epigenetic modifications such as DNA hypo- or hyper-methylation have been shown to occur in response to environmental exposures including dietary nutrients.MethodsWithin the context of the asthma randomized trial of indoor wood smoke (ARTIS) study, we investigated relationships between diet, asthma health measures, and DNA methylation. Asthma health measures included a quality of life instrument, diurnal peak flow variability (dPFV) and forced expiratory volume in the first second (FEV1). Dietary intake was assessed with a food frequency questionnaire. Methylation levels of LINE-1 repetitive element and two promoter CpG sites for interferon gamma (IFNγ, -186 and -54) from buccal cell DNA were measured using pyrosequencing assays.ResultsData were collected on 32 children with asthma living in western Montana who were recruited to the ARTIS study. Selenium and several methyl donor dietary nutrients were positively associated with the asthma quality of life measure. Intake of methyl donating nutrients including folate was positively associated LINE-1 methylation and negatively associated with IFNγ CpG-186. Higher levels of LINE-1 methylation were associated with greater dPFV.ConclusionWe identified several nutrients that were associated with improved quality of life measures among children with asthma. The IFNγ promoter CpG site -186 but not -54 was associated with the intake of selected dietary nutrients. However, in this small population of children with asthma, the IFNγ promoter CpG sites were not associated with respiratory health measures so it remains unclear through which epigenetic mechanism these nutrients are impacting the quality of life measure. These findings add to the evidence that dietary nutrients, particularly foods containing methyl donors, may be important for epigenetic regulation as it pertains to the control of asthma.Trial registration ClincialTrials.gov NCT00807183. Registered 10 December 2008
Highlights
Asthma is an increasingly common chronic disease among children, and data point toward a complex mechanism involving genetic, environmental and epigenetic factors
A subset of 32 children from the asthma randomized trial of indoor wood smoke (ARTIS) cohort participated in this study of diet, asthma health and epigenetics and was included in the analyses described here
We accounted for false discoveries, we recognize that several statistical tests were performed and would expect some significant results due to chance alone. These observations should be considered exploratory and requiring of further study in other populations. Within this cohort of childhood asthmatics, we sought to identify dietary nutrients that may be beneficial for respiratory health
Summary
Asthma is an increasingly common chronic disease among children, and data point toward a complex mechanism involving genetic, environmental and epigenetic factors. Epigenetic modifications such as DNA hypo- or hyper-methylation have been shown to occur in response to environmental exposures including dietary nutrients. Significant observational data suggests that dietary status and intake of particular nutrients can affect respiratory health outcomes. Several recent studies have suggested that some dietary nutrients may be protective for respiratory health [3,4,5,6,7,8,9,10,11,12]. In a mouse model of allergic airway disease, a combinatory therapeutic that included selenium attenuated the physiologic airway damage that is typical of this model [18]
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