Promoter methylation status of RORC , IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma.

A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of , , and . However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between , , and methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11-18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of , , and than the HP group. Notably, the OAP group presents lower promoter methylation status than the OP group. Interestingly, promoter methylation status was moderately negatively associated with gene expression of ( = -0.39, p 0.001) and ( = -0.37, p 0.01), respectively. Similarly, the promoter methylation pattern of was moderately negatively correlated with gene expression ( = -0.3, p 0.01). There is also a moderate inverse relationship between promoter methylation status and gene expression ( = -0.3, p 0.01). The present study suggests an association between lower , , and gene promoter methylation status with obesity-related asthma and allergic asthma. , and gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate C, , and gene expression in both asthmatic phenotypes.