1. Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan.
- Author
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Lin YJ, Chang JS, Liu X, Tsang H, Chien WK, Chen JH, Hsieh HY, Hsueh KC, Shiao YT, Li JP, Lin CW, Lai CH, Wu JY, Chen CH, Lin JG, Lin TH, Liao CC, Huang SM, Lan YC, Ho TJ, Liang WM, Yeh YC, Lin JC, and Tsai FJ
- Subjects
- Child, Preschool, China ethnology, Coronary Vessels pathology, Down-Regulation, Female, Gene Expression, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Infant, Interleukins genetics, Interleukins metabolism, KCNQ Potassium Channels genetics, KCNQ Potassium Channels metabolism, Male, Mucocutaneous Lymph Node Syndrome pathology, Phosphoinositide Phospholipase C genetics, Phosphoinositide Phospholipase C metabolism, Phospholipase C beta metabolism, Polymorphism, Single Nucleotide, Risk Factors, Taiwan, Coronary Aneurysm genetics, Mucocutaneous Lymph Node Syndrome genetics, Phospholipase C beta genetics
- 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.
- Published
- 2015
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