title: FCGR2A Promoter Methylation and Risks for Intravenous Immunoglobulin Treatment Responses in Kawasaki Disease.
abstract: Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause. The low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) gene was reported to be involved in the susceptibility of KD. DNA methylation is one of the epigenetic mechanisms that control gene expression; thus, we hypothesized that methylation status of CpG islands in FCGR2A promoter associates with the susceptibility and therapeutic outcomes of Kawasaki disease. In this study, 36 KD patients and 24 healthy subjects from out-patient clinic were recruited. Eleven potential methylation sites within the targeted promoter region of FCGR2A were selected for investigation. We marked the eleven methylation sites from A to K. Our results indicated that methylation at the CpG sites G, H, and J associated with the risk of KD. CpG sites B, C, E, F, H, J, and K were found to associate with the outcomes of IVIG treatment. In addition, CpG sites G, J, and K were predicted as transcription factors binding sites for NF-kB, Myc-Max, and SP2, respectively. Our study reported a significant association among the promoter methylation of FCGR2A, susceptibility of KD, and the therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter should be an important marker for optimizing IVIG therapy.
authors.affiliation: Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 80031, Taiwan.
authors.forename: Ho-Chang
authors.identifier: 0000-0002-3295-2984
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hsu
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Mei-Shin
authors.initials: MS
authors.lastname: Wu
authors.affiliation: Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan.
authors.forename: Peng Yeong
authors.initials: PY
authors.lastname: Woon
authors.affiliation: Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Henry Sung-Ching
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Li-Jen
authors.identifier: 0000-0002-4380-7440
authors.initials: LJ
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Ruo-Kai
authors.initials: RK
authors.lastname: Lin
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Sukhontip
authors.identifier: 0000-0001-9823-0733
authors.initials: S
authors.lastname: Klahan
authors.affiliation: Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 80031, Taiwan.
authors.forename: Kai-Sheng
authors.initials: KS
authors.lastname: Hsieh
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11696, Taiwan ; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 11696, Taiwan ; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80031, Taiwan ; Department of Pharmacy, Taipei Medical University-Wan Fang Hospital, Taipei 11696, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy* / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: C445323:FCGR2A protein, human; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG