title: Interferon-gamma Genetic Polymorphism and Expression in Kawasaki Disease.
abstract: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. IFNG gene encoding interferon (IFN)-γ, produced by natural killer cells and T cells, has been suggested to play an important role in the immunopathogenesis of Kawasaki disease. The aim of this study was to examin the correlation of gene polymorphisms of the IFNG gene and plasma levels of IFN-γ in KD patients and their outcomes.A total of 950 subjects (381 KD and 569 controls) were recruited. Three tagging single-nucleotide polymorphisms (rs2069718, rs1861493, rs2069705) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL), coronary artery aneurysms (CAA) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Plasma IFN-γ levels were also measured with an enzyme-linked immunosorbent assay.Polymorphisms of the IFNG gene were significantly different between the normal controls and KD patients. The G allele of rs1861493 conferred a better response to IVIG treatment in KD patients. AA allele frequencies of rs1861493 were also associated with a significantly higher risk of CAA in KD patients. Furthermore, the plasma IFN-γ level was lower in the AA allele than in the GG allele of rs1861493 both before and after IVIG treatment in KD patients.This study provides the first evidence supporting an association between IFNG gene polymorphisms, susceptibility of KD, IVIG responsiveness, and plasma IFN-γ levels in KD patients.
authors.affiliation: From the Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, (Y-HH, H-RY, F-CH, H-CK); Department of Clinical Pharmacy, Taipei Medical University (Y-WH, H-FL, W-CC); The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica (Y-WH); Department of Pharmacy, Taipei Medical University-Shuang Ho Hospital (H-FL, W-CC); Department of Clinical Pharmacy, College of Pharmacy, Taipei Medical University (HS-CW, W-CC); Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei (W-CC, H-CK); and Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Kaohsiung, Taiwan (H-CK).
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Huang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Hsu
authors.forename: Hsing-Fang
authors.initials: HF
authors.lastname: Lu
authors.forename: Henry Sung-Ching
authors.initials: HS
authors.lastname: Wong
authors.forename: Hong-Ren
authors.initials: HR
authors.lastname: Yu
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.forename: Fu-Chen
authors.initials: FC
authors.lastname: Huang
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
authors.forename: Ho-Chang
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007116:Immunization, Passive; D007223:Infant; D007371:Interferon-gamma / Q000097:blood* / Q000235:genetics*; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012016:Reference Values
chemical_list: D007371:Interferon-gamma