title: Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease.
abstract: BACKGROUND
  Kawasaki disease (KD) is a self limited vasculitis in which host genetics plays a prominent role. To further the understanding of the role of host genetics in KD, a three-stage genetic study was conducted that began with a family linkage study and ultimately involved more than 3000 individuals to identify new genetic contributions to KD susceptibility.
  
  
  RESULTS
  A 26-family linkage study followed by fine mapping was performed in a cohort of 1284 KD subjects and their family members (total 3248 individuals). Suggestive evidence of disease linkage (logarithm of odds (LOD) ≥3.0, p<1.00×10(-4)) was found for five genomic locations (Chr 3q, 4q, 10p, 13q, 21q). Two of these loci (Chr 4q and Chr 13q) overlapped with validated findings from a recent KD genome-wide association study. Fine mapping analysis revealed three single nucleotide polymorphisms (SNPs) in ATP-binding cassette, subfamily C, member 4 (ABCC4) underlying the Chr 13q linkage peak showing evidence of association to KD (lowest p=8.82×10(-5); combined OR 2.00, 95% CI 1.41 to 2.83). ABCC4 is a multifunctional cyclic nucleotide transporter that stimulates the migratory capacity of dendritic cells. It is also a mediator of prostaglandin efflux from human cells and is inhibited by non-steroidal anti-inflammatory medications such as aspirin.
  
  
  CONCLUSIONS
  These genetic data suggest that ABCC4 could play a fundamental role in KD pathogenesis with effects on immune activation and vascular response to injury.
authors.affiliation: Division of Infectious Diseases, Genome Institute of Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Sonia
authors.initials: S
authors.lastname: Davila
authors.forename: Chisato
authors.initials: C
authors.lastname: Shimizu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sheng
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Matsubara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Jane W
authors.initials: JW
authors.lastname: Newburger
authors.forename: Annette
authors.initials: A
authors.lastname: Baker
authors.forename: David
authors.initials: D
authors.lastname: Burgner
authors.forename: Willemijn
authors.initials: W
authors.lastname: Breunis
authors.forename: Taco
authors.initials: T
authors.lastname: Kuijpers
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Wright
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Jane C
authors.initials: JC
authors.lastname: Burns
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C073492:ABCC4 protein, human