CerS6 gene methylation in peripheral blood is associated with asthma and the frequent exacerbator phenotype

Background Sphingolipids metabolism regulated by ceramide synthase ( CerS ) enzyme is closely related to asthma development, but the underlying biological mechanism remains unclear. Given the critical role of epigenetics in the pathogenesis of asthma, we explored the DNA methylation patterns of CerS1-6 , the genes encoding the CerS enzyme, in asthma patients. Methods We enrolled 26 asthma patients and six healthy controls for this study. Peripheral blood samples were collected for the analysis of serum phospholipid profiles and DNA methylation assays. Linear regression models were employed to estimate DNA methylation dynamics of CerS1-6 genes between asthma patients and healthy controls, followed by bootstrap-based internal validation. Subgroup analyses were conducted for various asthma phenotypes. The correlation between the identified differentially methylated CpG sites and ceramide metabolites was further investigated. Results Among 127 CpG sites on CerS1-6 , four sites (cg18956199, cg21465008, cg03236449, and cg15455300) on CerS6 gene were significantly differentially methylated between asthma patients and healthy controls. Specifically, cg15455300 exhibited significantly lower methylation levels in asthma patients and was significantly associated with frequent asthma exacerbations and poor asthma control. Internal validation indicated robust and significant differences at locus cg18956199. We further observed varying degrees of correlation between ceramide metabolites and the methylation levels of the four identified CpG sites. A differentially methylated region (chr2: 169311373–169312695) located on CerS6 was also identified. Conclusion Our study offered potential insights into asthma pathogenesis by revealing distinct DNA methylation patterns across CerS6 gene between asthma patients and healthy controls.