Polymorphisms of transforming growth factor-β signaling pathway and Kawasaki disease in the Taiwanese population

Kawasaki disease (KD) is a systemic vasculitis associated with cardiovascular symptom. A previous study in the European descent has indicated that genetic variants of the transforming growth factor-β (TGF-β) pathway are involved in the KD susceptibility and clinical status. This study was conducted to investigate if polymorphisms in TGF-β signaling pathway are associated with KD susceptibility, and the coronary artery lesion formation. A total of 950 subjects (381 KD patients and 569 controls) were investigated to identify 12 single-nucleotide polymorphisms in the TGF-β signaling pathway (rs2796817, rs10482751, rs2027567, rs12029576, rs11466480, rs4776338, rs12901071, rs7162912, rs1438386, rs6494633, rs12910698 and rs4776339) by using TaqMan Allelic Discrimination assay. Our results indicated that rs1438386 in the SMAD3 is significantly associated with the susceptibility of KD. Additionally, both haplotypes of TGFβ2 and SMAD3 were also associated with the risk of KD. This study showed that genetic polymorphisms in TGF-β signaling pathway are associated with KD susceptibility, but not coronary artery lesions formation, or intravenous immunoglobulin treatment response in the Taiwanese population.

[1]  Walter R Wilson,et al.  Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association , 2004, Pediatrics.

[2]  K. Kayaba,et al.  Increasing incidence of Kawasaki disease in Japan: Nationwide survey , 2008, Pediatrics international : official journal of the Japan Pediatric Society.

[3]  Chien-Fu Huang,et al.  CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children , 2011, Journal of Human Genetics.

[4]  Lei Wan,et al.  Interleukin‐18 gene 105A/C genetic polymorphism is associated with the susceptibility of Kawasaki disease , 2009, Journal of clinical laboratory analysis.

[5]  Kuender D Yang,et al.  A unique plasma proteomic profiling with imbalanced fibrinogen cascade in patients with Kawasaki disease , 2009, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[6]  Pei-Jer Chen,et al.  Epidemiologic Features of Kawasaki Disease in Taiwan, 2003–2006 , 2009, Pediatrics.

[7]  Yusuke Nakamura,et al.  CD40 ligand gene and Kawasaki disease , 2004, European Journal of Human Genetics.

[8]  Chien-Fu Huang,et al.  Association of lower eosinophil‐related T helper 2 (Th2) cytokines with coronary artery lesions in Kawasaki disease , 2009, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[9]  Fuu-Jen Tsai,et al.  Identification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study , 2011, PloS one.

[10]  A. Kulkarni,et al.  Immune dysregulation in TGF-beta 1-deficient mice. , 1994, Journal of immunology.

[11]  Andrew W. Taylor.  Review of the activation of TGF‐β in immunity , 2008, Journal of leukocyte biology.

[12]  Jong-Keuk Lee,et al.  The CCR5 (−2135C/T) Polymorphism may be Associated with the Development of Kawasaki Disease in Korean Children , 2008, Journal of Clinical Immunology.

[13]  Andrew Leask,et al.  TGF‐β signaling and the fibrotic response , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  Kao-Pin Hwang,et al.  Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease , 2010, Acta paediatrica.

[15]  Kuender D Yang,et al.  The relationship of eosinophilia to intravenous immunoglobulin treatment failure in Kawasaki disease , 2007, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[16]  Anbupalam Thalamuthu,et al.  A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease , 2009, PLoS genetics.

[17]  Y. Kohno,et al.  Monocyte chemoattractant protein 1 gene regulatory region polymorphism and serum levels of monocyte chemoattractant protein 1 in Japanese patients with Kawasaki disease. , 2001, Arthritis and rheumatism.

[18]  I. Park,et al.  Kawasaki Disease in Korea, 2003–2005 , 2007, The Pediatric infectious disease journal.

[19]  Xianlin Han,et al.  Cholesterol suppresses cellular TGF-β responsiveness: implications in atherogenesis , 2007, Journal of Cell Science.

[20]  Kuender D Yang,et al.  Kawasaki disease: infection, immunity and genetics. , 2005, The Pediatric infectious disease journal.

[21]  Scott Mellis,et al.  Transforming Growth Factor-&bgr; Signaling Pathway in Patients With Kawasaki Disease , 2011, Circulation. Cardiovascular genetics.

[22]  I-Chun Lin,et al.  ITPKC Single Nucleotide Polymorphism Associated with the Kawasaki Disease in a Taiwanese Population , 2011, PloS one.

[23]  A. Levine,et al.  TGF-β Inhibits IL-2 Production and Promotes Cell Cycle Arrest in TCR-Activated Effector/Memory T Cells in the Presence of Sustained TCR Signal Transduction1 , 2008, The Journal of Immunology.

[24]  Yusuke Nakamura,et al.  Common variants in CASP3 confer susceptibility to Kawasaki disease. , 2010, Human molecular genetics.

[25]  R. Cantor,et al.  Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease , 2005, Genes and Immunity.

[26]  Yeon-Su Lee,et al.  A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease , 2011, Human Genetics.

[27]  I-Chun Lin,et al.  CTLA-4, Position 49 A/G Polymorphism Associated with Coronary Artery Lesions in Kawasaki Disease , 2011, Journal of Clinical Immunology.

[28]  Kuender D Yang,et al.  Persistent monocytosis after intravenous immunoglobulin therapy correlated with the development of coronary artery lesions in patients with Kawasaki disease. , 2007, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[29]  Kuender D Yang,et al.  Coronary artery fistula associated with Kawasaki disease. , 2009, American heart journal.

[30]  Yusuke Nakamura,et al.  ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms , 2008, Nature Genetics.

[31]  H. Yanagawa,et al.  A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. , 1974, Pediatrics.

[32]  Kai-Sheng Hsieh,et al.  IL-10 polymorphisms are associated with coronary artery lesions in acute stage of Kawasaki disease. , 2010, Circulation journal : official journal of the Japanese Circulation Society.