title: FcγR gene copy number in Kawasaki disease and intravenous immunoglobulin treatment response.
abstract: OBJECTIVE
  Kawasaki disease (KD), response to intravenous immunoglobulin (IVIG) therapy, and associated coronary artery disease progression have been associated with genetic polymorphisms in Fc gamma receptor (FcγR) genes. However, it is not known whether the existing gene copy number (GCN) variability relates to KD treatment response, susceptibility, or associated sequelae.
  
  
  METHODS
  The copy number of individuals with KD (n=510) and their family members (n=808) for three variable FcγRs was assessed using pyrosequencing. We performed the transmission disequilibrium test to examine the association of GCN for FcγRs (FcγR2C, FcγR3A, and FcγR3B) with susceptibility and used logistic regression models to determine its association with IVIG treatment outcomes.
  
  
  RESULTS
  FcγR2C and FcγR3B GCN were significantly associated with KD susceptibility. IVIG response was associated with GCN variations of FcγR3B in Whites and FcγR2C in Hispanics, and gene risk score based on single nucleotide polymorphism and GCN in FcγRs were significantly different between IVIG responders and nonresponders among Whites. We found no significant associations between coronary artery disease and any of the FcγR copy numbers.
  
  
  CONCLUSIONS
  GCN of FcγR2C and FcγR3B influences IVIG treatment response and predisposes individuals to KD, providing potential insights into understanding the mechanism of the FcγR gene family in the IVIG pathway.
authors.affiliation: Department of Biostatistics, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Makowsky
authors.forename: Howard W
authors.initials: HW
authors.lastname: Wiener
authors.forename: Travis S
authors.initials: TS
authors.lastname: Ptacek
authors.forename: Miriam
authors.initials: M
authors.lastname: Silva
authors.forename: Aditi
authors.initials: A
authors.lastname: Shendre
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Edberg
authors.forename: Michael A
authors.initials: MA
authors.lastname: Portman
authors.forename: Sadeep
authors.initials: S
authors.lastname: Shrestha
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000628:therapy*; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
chemical_list: D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG