Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause and the Fc Fragment of IgG, Low Affinity IIa, Receptor (FCGR2A) gene was reported to involve in increasing susceptibility of KD. Because DNA methylation is one of the epigenetic mechanisms that control gene expression, we hypothesized that methylation status of CpG islands in FCGR2A promoter predisposes an individual to Kawasaki disease.
We recruited 36 KD patients and 24 healthy subjects with informed consents. And eleven potential methylation loci within the targeted promoter region (chr1:161474603-161475102) of Fc Fragment of IgG, Low Affinity IIa, Receptor were selected for investigation.
Methylation at the CpG sites G, H and J displayed a strongly associations with KD, whereas CpG sites B,C,E,F,H,J and K were found to be correlated with non-responsive to IVIG treatment. In addition, CpG sites G, J and K were predicted as the significant transcription factor binding site for NF-kB, Myc-Max and SP2 respectively.
Our study reports a significant association between the promoter methylation of FCGR2A, susceptibility of Kawasaki disease and therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter may be an important marker for optimizing IVIG therapy.