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.
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Children's Hospital of China Medical University, Taichung, Taiwan.|School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Jeng-Sheng
authors.initials: JS
authors.lastname: Chang
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hsinyi
authors.initials: H
authors.lastname: Tsang
authors.affiliation: Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wen-Kuei
authors.initials: WK
authors.lastname: Chien
authors.affiliation: Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan.|School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Children's Hospital of China Medical University, Taichung, Taiwan.|Pediatric Emergency Division of Children's Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Hsin-Yang
authors.initials: HY
authors.lastname: Hsieh
authors.affiliation: Kai-Chung Hsueh Clinics, Taichung, Taiwan.
authors.forename: Kai-Chung
authors.initials: KC
authors.lastname: Hsueh
authors.affiliation: Heart Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Tzone
authors.initials: YT
authors.lastname: Shiao
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Rheumatism Research Center, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ju-Pi
authors.initials: JP
authors.lastname: Li
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ting-Hsu
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chiu-Chu
authors.initials: CC
authors.lastname: Liao
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Shao-Mei
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Health Risk Management, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lan
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Miin
authors.initials: WM
authors.lastname: Liang
authors.affiliation: Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Yeh
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jung-Chun
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D002675:Child, Preschool; D002681:China / Q000208:ethnology; D003323:Coronary Aneurysm / Q000235:genetics*; D003331:Coronary Vessels / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051656:KCNQ Potassium Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000473:pathology; D054801:Phosphoinositide Phospholipase C / Q000235:genetics / Q000378:metabolism; D054799:Phospholipase C beta / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013624:Taiwan
chemical_list: D007378:Interleukins; D051656:KCNQ Potassium Channels; C412231:KCNQ5 protein, human; C518033:PLCB1 protein, human; C518042:PLCB4 protein, human; D054801:Phosphoinositide Phospholipase C; D054799:Phospholipase C beta; C423320:phospholipase C epsilon