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Background/aims: Pediatric inflammatory bowel disease (IBD) has been increasing worldwide. The characteristics of pediatric-onset IBD have mainly been reported in Western countries. We investigated the clinical characteristics of pediatric IBD in Korea and compared these with the data from the 5-year European multicenter study of children with new-onset IBD (EUROKIDS registry)., Methods: Children who were diagnosed with IBD between July 1987 and January 2012 were investigated at five Korean university hospitals. Their clinical characteristics were retrospectively evaluated by medical record review. The results were compared with the EUROKIDS data., Results: A total of 30 children with Crohn's disease (CD) and 33 children with ulcerative colitis (UC) were enrolled. In comparison with the EUROKIDS group, Korean pediatric IBD patients showed a male predominance (86.7% vs 59.2%, p=0.002 in CD; 75.8% vs 50%, p=0.003 in UC). Korean pediatric CD patients had a higher prevalence of terminal ileal disease (36.7% vs 16.3%, p=0.004) and perianal disease (33.3% vs 8.2%, p<0.001) than patients in the EUROKIDS group. Korean pediatric UC patients had a higher prevalence of proctitis than patients in the EUROKIDS group., Conclusions: Our results suggest that the characteristics of Korean pediatric IBD patients and European pediatric IBD patients may be different.

Objective: Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA., Approach and Results: Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0×10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9×10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3×10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0×10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0×10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke., Conclusions: We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.