Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan

Ying Ju Lin, Jeng Sheng Chang, Xiang Liu, Hsinyi Tsang, Wen Kuei Chien, Jin Hua Chen, Hsin Yang Hsieh, Kai Chung Hsueh, Yi Tzone Shiao, Ju Pi Li, Cheng Wen Lin, Chih Ho Lai, Jer Yuarn Wu, Chien Hsiun Chen, Jaung Geng Lin, Ting Hsu Lin, Chiu Chu Liao, Shao Mei Huang, Yu Ching Lan, Tsung Jung HoWen Miin Liang, Yi Chun Yeh, Jung Chun Lin, Fuu Jen Tsai

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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.

Original languageEnglish
Article number14762
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Oct 5 2015

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    Lin, Y. J., Chang, J. S., Liu, X., Tsang, H., Chien, W. K., Chen, J. H., Hsieh, H. Y., Hsueh, K. C., Shiao, Y. T., Li, J. P., Lin, C. W., Lai, C. H., Wu, J. Y., Chen, C. H., Lin, J. G., Lin, T. H., Liao, C. C., Huang, S. M., Lan, Y. C., ... Tsai, F. J. (2015). Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan. Scientific Reports, 5, [14762]. https://doi.org/10.1038/srep14762