Details

Autor(en) / Beteiligte

• Khor, Chiea Chuen
• Davila, Sonia
• Shimizu, Chisato
• Sheng, Stephanie
• Matsubara, Tomoyo
• Suzuki, Yasuo
• Newburger, Jane W
• Baker, Annette
• Burgner, David
• Breunis, Willemijn
• Kuijpers, Taco
• Wright, Victoria J
• Levin, Michael
• Hibberd, Martin L
• Burns, Jane C

Titel

Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease

Ist Teil von

• Journal of medical genetics, 2011-07, Vol.48 (7), p.467-472

Ort / Verlag

London: BMJ Publishing Group Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

BMJ Journals Archiv - DFG Nationallizenzen

Beschreibungen/Notizen

• BackgroundKawasaki 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 resultsA 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.ConclusionThese genetic data suggest that ABCC4 could play a fundamental role in KD pathogenesis with effects on immune activation and vascular response to injury.