@article{ddd3eddee1eb4a8da5c0ab25842514db,
title = "Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan",
abstract = "Kawasaki disease (KD) is an acute, inflammatory, and self-limited vasculitis affecting infants and young children. Coronary artery aneurysm (CAA) formation is the major complication of KD and the leading cause of acquired cardiovascular disease among children. To identify susceptible loci that might predispose patients with KD to CAA formation, a genome-wide association screen was performed in a Taiwanese KD cohort. Patients with both KD and CAA had longer fever duration and delayed intravenous immunoglobulin treatment time. After adjusting for these factors, 100 susceptibility loci were identified. Four genes were identified from a single cluster of 35 using the Ingenuity Pathway Analysis (IPA) Knowledge Base. Silencing KCNQ5, PLCB1, PLCB4, and PLCL1 inhibited the effect of lipopolysaccharide-induced endothelial cell inflammation with varying degrees of proinflammatory cytokine expression. PLCB1 showed the most significant inhibition. Endothelial cell inflammation was also inhibited by using a phospholipase C (PLC) inhibitor. The single nucleotide polymorphism rs6140791 was identified between PLCB4 and PLCB1. Plasma PLC levels were higher in patients with KD and CC+CG rs6140791genotypes, and these genotypes were more prevalent in patients with KD who also had CAA. Our results suggest that polymorphism of the PLCB4/B1 genes might be involved in the CAA pathogenesis of KD.",
author = "Lin, {Ying Ju} and Chang, {Jeng Sheng} and Xiang Liu and Hsinyi Tsang and Chien, {Wen Kuei} and Chen, {Jin Hua} and Hsieh, {Hsin Yang} and Hsueh, {Kai Chung} and Shiao, {Yi Tzone} and Li, {Ju Pi} and Lin, {Cheng Wen} and Lai, {Chih Ho} and Wu, {Jer Yuarn} and Chen, {Chien Hsiun} and Lin, {Jaung Geng} and Lin, {Ting Hsu} and Liao, {Chiu Chu} and Huang, {Shao Mei} and Lan, {Yu Ching} and Ho, {Tsung Jung} and Liang, {Wen Miin} and Yeh, {Yi Chun} and Lin, {Jung Chun} and Tsai, {Fuu Jen}",
note = "Funding Information: This study was supported by grants from the China Medical University (CMU102-PH-01 and CMU100-S-01), the China Medical University Hospital (DMR-102-083, DMR-104-029, and DMR-104-089), the National Science Council, the Ministry of Science and Technology, Taiwan (NSC101-2314-B-039-008-MY3, NSC 102-2314-B-039 -011 -MY3, and MOST 103-2320-B-039 -006 -MY3), and China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan. We thank the National Center for Genome Medicine of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, for technical and bioinformatics support. We also thank Drs. Ya-Hui Chi, Kuan-Teh Jeang, and Willy W.L. Hong for technical help and suggestions.",
year = "2015",
month = oct,
day = "5",
doi = "10.1038/srep14762",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Research",
}