Abstract 37: Consortium-Based Genetic Studies of Kawasaki Disease in Korea

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In order to perform large-scale genetic studies of Kawasaki disease (KD) in Korea, the Korean Kawasaki Disease Genetics Consortium (KKDGC) was formed in 2008 with 10 hospitals. Since the establishment of KKDGC, we have collected a total of 1,198 patients’ clinical data and approximately 5 ml of blood samples per patient (for genomic DNA and plasma isolation) using standard clinical data collection forms and nation-wide networking system for blood sample pick-up. In our previous clinical risk factor analysis using collected clinical data of 478 KD patients, we found that incomplete KD, intravenous immunoglobulin (IVIG) non-responsiveness, long febrile days are major risk factors for coronary artery lesions (CALs) development, whereas low serum albumin concentration is an independent risk factor for IVIG non-responsiveness. Recently, we are re-analyzing the clinical data of all collected KD patients to evaluate the effect of age, gender, family history status, recurrence status, KD types on clinical features of KD. In addition, in our previous genome-wide association studies (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls, we identified a Kawasaki disease susceptibility locus at 1p31. We also identified significant associations of coronary artery aneurysm with a variant located in KCNN2 gene and common variants in CRP gene promoter with the increased CRP levels in KD patients. Furthermore, to identify new KD susceptibility and subphenotype loci, we are performing another GWAS using Illumina Human Omni1 SNP chip with approximately 300 KD cases containing 16 cases with family history, 46 cases with recurrence, 119 cases with IVIG non-responsiveness, 52 cases with CALs (diameter >5mm). Multiple subsets of KD cases will be very useful to detect loci associated with the subphenotypes of KD in GWAS data analysis. We also performed DNA microarray analysis to determine differential gene expression by in vitro immunoglobulin treatment using patient-derived B cell lines (IVIG-responders vs. IVIG-non-responders). However, we could not find any difference between B cell lines. Furthermore, a pilot study of exome sequencing of 12 KD cases was not successful in identifying causal KD susceptibility genes.

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