Methylation Landscape of RUNX3 Promoter Region as a Predictive Marker for Th1/Th2 Imbalance in Bronchiolitis.

ABSTRACT

BACKGROUND The methylation status of RUNX3 promoter region, its impact on RUNX3 gene expression, and Th1/Th2 imbalance are unknown in bronchiolitis. This study aimed to explore the predictors of bronchiolitis developing into asthma. MATERIAL AND METHODS The methylation status of RUNX3 promoter was assessed using Illumina HiSeq platform method. The relative RUNX3 mRNA levels in PBMCs were measured by qRT-PCR. Serum IL-4 and IFN-γ concentrations were measured by ELISA. RESULTS A series of sites with significantly higher levels of methylation as compared to their corresponding controls were identified, including 24 sites in group Ba vs. group Cn, 13 sites in group Ba vs. group Ca, 7 sites in group Ba vs. group Bn, 16 sites in group Bn vs. group Cn, 11 sites in group Ca vs. group Cn, and 23 sites in group B vs. group C; P<0.05. The relative mRNA levels in group Ba were significantly lower than those in groups Cn, Ca, Bn; P<0.05. The serum IL-4 concentrations in group Ba were significantly higher than those in group Cn; P<0.05. The serum IFN-γ concentrations in group Ba were significantly lower than those in groups Cn, Ca, Bn; P<0.05. Correlation analysis showed that differentially methylated RUNX3 promoter region sites were significantly negatively correlated with levels of relative RUNX3 mRNA and IFN-γ, and were significantly positively correlated with IL-4 levels. CONCLUSIONS The methylation status of RUNX3 promoter region plays a role in Th1/Th2 imbalance by silencing RUNX3 gene expression, which can serve as predictive marker for the development of bronchiolitis into asthma.