%0 Journal Article %A Chiea Chuen Khor %A Sonia Davila %A Chisato Shimizu %A Stephanie Sheng %A Tomoyo Matsubara %A Yasuo Suzuki %A Jane W Newburger %A Annette Baker %A David Burgner %A Willemijn Breunis %A Taco Kuijpers %A Victoria J Wright %A Michael Levin %A Martin L Hibberd %A Jane C Burns %A on behalf of the US and International Kawasaki Disease Genetics Consortia %T Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease %D 2011 %R 10.1136/jmg.2010.086611 %J Journal of Medical Genetics %P 467-472 %V 48 %N 7 %X 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.Methods and 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.Conclusion These genetic data suggest that ABCC4 could play a fundamental role in KD pathogenesis with effects on immune activation and vascular response to injury. %U https://jmg.bmj.com/content/jmedgenet/48/7/467.full.pdf