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\begin{document}

\title{CerS6 gene methylation in peripheral blood is associated with asthma and
the frequent exacerbator phenotype}



\author[1]{Zhu Song}%
\author[2]{Yuting Wang}%
\author[1]{Heqing Huang}%
\author[1]{Tingting Hu}%
\author[2]{Xu Gao}%
\author[1]{Chun Chang}%
\affil[1]{Peking University Third Hospital}%
\affil[2]{Peking University Department of Occupational and Environmental Health Sciences}%


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  \date{May 27, 2024}


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\begin{abstract}
\textbf{Background} Sphingolipids metabolism regulated by ceramide
synthase (CerS) enzyme is closely related to asthma development, but the
underlying biological mechanism remains unclear. Since epigenetics plays
a critical role in the pathogenesis of asthma, we thus studied the DNA
methylation of \emph{CerS1-6}, genes coding CerS in asthma patients.
\textbf{Methods} We enrolled 26 asthma patients and 6 healthy controls.
After collecting demographic and clinical information, peripheral blood
was collected to analyze the serum phospholipid profile and DNA
methylation assay. Illumina Human Methylation EPIC BeadChip (Illumina,
USA) was used to perform DNA methylation profiling. Linear mixed-effect
models were applied to estimate the associations between asthma patients
and healthy controls. Subgroup analyses by different asthma phenotypes,
frequent acute exacerbation, levels of asthma control, overweight,
allergic, early onset, and different genders were further conducted.
\textbf{Results} Among 127 CpG sites mapped on \emph{CerS1-6,} we found
that four sites including cg18956199, cg21465008, cg03236449 and
cg15455300 located on \emph{Cers6} genes were significantly
differentiated in asthma patients. Particularly, the locus cg15455300
had significantly lower methylation levels in asthma patients compared
to controls. After controlling for potential covariates, compared to
healthy control, the DNA methylation level of cg15455300 decreased
0.0202 (Standard error = 0.0055) robustly. This site further associated
with patients with frequent acute exacerbation and poorly controlled
asthma. A negative correlation between cg15455300 and ceramide
metabolites was further observed. \textbf{Conclusion} Changes in CerS6
gene methylation in blood have the potential to serve as a surrogate
biomarker for asthma and frequent acute exacerbation phenotypes.%
\end{abstract}%



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