Nasal DNA methylation may predict response to systemic steroid treatment
Methylation of nasal DNA may identify responders to acute systemic steroid treatment in paediatric patients with asthma, independent of single nucleotide polymorphisms (SNPs), according to a recent study.
The investigators divided 33 paediatric patients aged 5 to 18 years who had asthma exacerbations into two according to response to steroid treatment: good responders (n=15; median age 8.0 years; 67 percent male) and poor responders (n=18; median age 6.5 years; 67 percent male). Nasal samples collected at presentation (T0) and at 18 to 24 hours after (T1) were used to determine DNA methylation.
DNA methylation at CpG sites did not change between T0 and T1 in poor responders. On the other hand, five CpG sites in good responders showed nominally significantly altered DNA methylation, which did not reach genome-wide significance.
Using data from the T1 nasal samples, 85 CpG sites showed differential DNA methylation between the groups and were able to determine poor from good systemic steroid treatment responders. The level of methylation in 32 of these sites was enough to completely distinguish between the two groups.
Pathway analysis showed that some of these 32 sites were in the promoter of the LDHC gene, which codes for lactate dehydrogenase. At these sites, methylation correlated negatively with gene expression.
“Interestingly, quite a few of these CpG sites can be disrupted by the presence of certain common SNPs; in most of these sites, DNA methylation was altered along with their genotypes,” researchers said.
“Taken together, our findings suggest that epigenetic mechanisms underlie the heterogeneous responses to systemic steroid treatment, in part driven by genetic variations present at CpG sites,” they added.