title: The roles of Ca2+/NFAT signaling genes in Kawasaki disease: single- and multiple-risk genetic variants.
abstract: Ca(2+)/nuclear factor of activated T-cells (Ca(2+)/NFAT) signaling pathway may play a crucial role in Kawasaki disease (KD). We investigated 16 genetic variants, selected by bioinformatics analyses or previous studies, in 7 key genes involved in this pathway in a Chinese population. We observed a significantly or marginally increased KD risk associated with rs2720378 GC + CC genotypes (OR = 1.39, 95% CI = 1.07-1.80, P = 0.014) or rs2069762 AC + CC genotypes (OR = 1.28, 95% CI = 0.98-1.67, P = 0.066), compared with their wild type counterparts. In classification and regression tree analysis, individuals carrying the combined genotypes of rs2720378 GC or CC genotype, rs2069762 CA or CC genotype and rs1561876 AA genotype exhibited the highest KD risk (OR = 2.12, 95% CI = 1.46-3.07, P < 0.001), compared with the lowest risk carriers of rs2720378 GG genotype. Moreover, a significant dose effect was observed among these three variants (Ptrend < 0.001). In conclusion, this study implicates that single- and multiple-risk genetic variants in this pathway might contribute to KD susceptibility. Further studies on more comprehensive single nucleotide polymorphisms, different ethnicities and larger sample sizes are warranted, and the exact biological mechanisms need to be further clarified.
authors.affiliation: 1] Children's Hospital, Zhejiang University School of Medicine, Hangzhou, PR China [2].
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1] Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China [2].
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Children's Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: Yan-qi
authors.initials: YQ
authors.lastname: Qi
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Shen
authors.affiliation: Guangdong Women and Children Hospital, Guangzhou, PR China.
authors.forename: Xu-zai
authors.initials: XZ
authors.lastname: Lu
authors.affiliation: Centre Hospitalier de l'Université de Montréal, CRCHUM-Hôpital Notre-Dame, Pavillion DeSève, Montreal, Canada.
authors.forename: Yu-jia
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Children's Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Jia-yu
authors.initials: JY
authors.lastname: Duan
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Jun-tao
authors.initials: JT
authors.lastname: Ke
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Miao
authors.affiliation: Children's Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
authors.forename: Fang-qi
authors.initials: FQ
authors.lastname: Gong
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D050778:NFATC Transcription Factors / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D050778:NFATC Transcription Factors; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; C505407:CASP3 protein, human; D053148:Caspase 3