PT - JOURNAL ARTICLE AU - Chiea Chuen Khor AU - Sonia Davila AU - Chisato Shimizu AU - Stephanie Sheng AU - Tomoyo Matsubara AU - Yasuo Suzuki AU - Jane W Newburger AU - Annette Baker AU - David Burgner AU - Willemijn Breunis AU - Taco Kuijpers AU - Victoria J Wright AU - Michael Levin AU - Martin L Hibberd AU - Jane C Burns AU - on behalf of the US and International Kawasaki Disease Genetics Consortia TI - Genome-wide linkage and association mapping identify susceptibility alleles in <em>ABCC4</em> for Kawasaki disease AID - 10.1136/jmg.2010.086611 DP - 2011 Jul 01 TA - Journal of Medical Genetics PG - 467--472 VI - 48 IP - 7 4099 - http://jmg.bmj.com/content/48/7/467.short 4100 - http://jmg.bmj.com/content/48/7/467.full SO - J Med Genet2011 Jul 01; 48 AB - 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&lt;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.