Abstract
BackgroundAsthma is associated with allergic sensitization in about half of all cases, and asthma phenotypes can vary by age and sex. DNA methylation in the promoter of the allergy regulatory gene interferon gamma (IFNγ) has been linked to the maintenance of allergic immune function in human cell and mouse models. We hypothesized that IFNγ promoter methylation at two well-studied, key cytosine phosphate guanine (CpG) sites (-186 and -54), may differ by age, sex, and airway versus systemic tissue in a cohort of 74 allergic asthmatics.ResultsAfter sampling buccal cells, a surrogate for airway epithelial cells, and CD4+ lymphocytes, we found that CD4+ lymphocyte methylation was significantly higher in children compared to adults at both CpG sites (P <0.01). Buccal cell methylation was significantly higher in children at CpG -186 (P = 0.03) but not CpG -54 (P = 0.66). Methylation was higher in males compared to females at both CpG sites in CD4+ lymphocytes (-186: P <0.01, -54: P = 0.02) but not buccal cells (-186: P = 0.14, -54: P = 0.60). In addition, methylation was lower in CD4+ lymphocytes compared to buccal cells (P <0.01) and neighboring CpG sites were strongly correlated in CD4+ lymphocytes (r = 0.84, P <0.01) and weakly correlated in buccal cells (r = 0.24, P = 0.04). At CpG -186, there was significant correlation between CD4+ lymphocytes and buccal cells (r = 0.24, P = 0.04) but not at CpG -54 (r = -0.03, P = 0.78).ConclusionsThese findings highlight significant age, sex, and tissue-related differences in IFNγ promoter methylation that further our understanding of methylation in the allergic asthma pathway and in the application of biomarkers in clinical research.
Highlights
Asthma is associated with allergic sensitization in about half of all cases, and asthma phenotypes can vary by age and sex
The methylation of CD4+ lymphocytes was higher in males compared with females at both cytosine phosphate guanine (CpG) −186 (P
As age in males increased by one year absolute CD4+ lymphocyte methylation decreased by 0.52%, whereas as age in females increased by one year absolute methylation decreased by 0.28%
Summary
Asthma is associated with allergic sensitization in about half of all cases, and asthma phenotypes can vary by age and sex. DNA methylation in the promoter of the allergy regulatory gene interferon gamma (IFNγ) has been linked to the maintenance of allergic immune function in human cell and mouse models. Hypermethylation of IFNγ was positively correlated with proallergic immunoglobulin E (IgE) [14] and associated with protection from allergic inflammation and reduction in airway hyperreactivity in experimental versus control mice [15]. This relationship was investigated further both in vitro and in human cell experiments by Tang et al [16]. IFNγ methylation has been shown to vary by asthma diagnosis among monozygotic twins consistent with mediation by environmental exposure [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
