CD40 Gene Polymorphisms Associated with Susceptibility and Coronary Artery Lesions of Kawasaki Disease in the Taiwanese Population

Background. Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. Our previous studies showed expression of CD40 ligand on CD4+ T cells correlated to the coronary artery lesion (CAL) and disease progress in KD. Other studies from Japan suggested the role of CD40L in the pathogenesis of CAL, and this might help explain the excessive number of males affected with KD but cannot be reproduced by Taiwanese population. This study was conducted to investigate the CD40 polymorphism in KD and CAL formation. Methods. A total of 950 subjects (381 KD patients and 569 controls) were investigated to identify 2 tagging single-nucleotide polymorphisms (tSNPs) of CD40 (rs4810485 and rs1535045) by using the TaqMan allelic discrimination assay. Results. A significant association was noted with regards to CD40 tSNPs (rs1535045) between controls and KD patients (P = 0.0405, dominant model). In KD patients, polymorphisms of CD40 (rs4810485) showed significant association with CAL formation (P = 0.0436, recessive model). Haplotype analysis did not yield more significant results between polymorphisms of CD40 and susceptibility/disease activity of KD. Conclusions. This study showed for the first time that polymorphisms of CD40 are associated with susceptibility to KD and CAL formation, in the Taiwanese population.

[1]  Lei Wan,et al.  Influence of interleukin 18 promoter polymorphisms in susceptibility to Kawasaki disease in Taiwan. , 2008, The Journal of rheumatology.

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

[3]  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.

[4]  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.

[5]  C. Langefeld,et al.  Variants of the CD40 gene but not of the CD40L gene are associated with coronary artery calcification in the Diabetes Heart Study (DHS). , 2006, American heart journal.

[6]  Mei-Chyn Chao,et al.  Polymorphisms of transforming growth factor-β signaling pathway and Kawasaki disease in the Taiwanese population , 2011, Journal of Human Genetics.

[7]  T Enright,et al.  Kawasaki syndrome. , 1990, Annals of allergy.

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

[9]  J. Mehta,et al.  LOX-1, an Oxidized LDL Endothelial Receptor, Induces CD40/CD40L Signaling in Human Coronary Artery Endothelial Cells , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[10]  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, Circulation.

[11]  E. Shapiro,et al.  Association between a Novel Human Coronavirus and Kawasaki Disease , 2005, The Journal of infectious diseases.

[12]  H. Takada,et al.  Th1 and Th2 cytokine production is suppressed at the level of transcriptional regulation in Kawasaki disease , 2004, Clinical and experimental immunology.

[13]  Kuender D Yang,et al.  Lack of Association between ORAI1/CRACM1 Gene Polymorphisms and Kawasaki Disease in the Taiwanese Children , 2011, Journal of Clinical Immunology.

[14]  Kuender D Yang,et al.  Decreased nitric oxide production after intravenous immunoglobulin treatment in patients with Kawasaki disease. , 2002, The Journal of pediatrics.

[15]  L. Jonides,et al.  Kawasaki disease. , 1994, Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners.

[16]  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.

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

[18]  Reinhold Förster,et al.  CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells , 1998, Nature.

[19]  B. Berkhout,et al.  Lack of Association between Infection with a Novel Human Coronavirus (HCoV), HCoV-NH, and Kawasaki Disease in Taiwan , 2006, The Journal of infectious diseases.

[20]  T Kobayashi,et al.  Increased CD11b expression on polymorphonuclear leucocytes and cytokine profiles in patients with Kawasaki disease , 2007, Clinical and experimental immunology.

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

[22]  T. Ebihara,et al.  Lack of Association between New Haven Coronavirus and Kawasaki Disease , 2005, The Journal of infectious diseases.

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

[24]  Kuender D Yang,et al.  Expression of CD40 ligand on CD4+ T-cells and platelets correlated to the coronary artery lesion and disease progress in Kawasaki disease. , 2003, Pediatrics.

[25]  C. Stefanadis,et al.  The CD40/CD40 ligand system: linking inflammation with atherothrombosis. , 2009, Journal of the American College of Cardiology.

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

[27]  B. Pamukcu,et al.  The CD40-CD40L system in cardiovascular disease , 2011, Annals of medicine.

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

[29]  A. Nezos,et al.  CD40/CD40L signaling and its implication in health and disease , 2009, BioFactors.

[30]  Shih-Feng Tsai,et al.  IL-10 Promoter Genetic Polymorphisms and Risk of Kawasaki Disease in Taiwan , 2011, Disease markers.

[31]  Hack‐Ki Kim,et al.  Kawasaki disease in Korea , 1992 .

[32]  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.

[33]  F. Huang,et al.  Genetic Polymorphisms in the CD40 Ligand Gene and Kawasaki Disease , 2008, Journal of Clinical Immunology.

[34]  Stefanie Dimmeler,et al.  CD40 and vascular inflammation. , 2004, The Canadian journal of cardiology.

[35]  Hiroyuki Ohashi,et al.  Elevated Levels of High-Sensitivity C-Reactive Protein and Serum Amyloid-A Late After Kawasaki Disease: Association Between Inflammation and Late Coronary Sequelae in Kawasaki Disease , 2005, Circulation.

[36]  Shoichi Ozaki,et al.  A novel anti‐peroxiredoxin autoantibody in patients with Kawasaki disease , 2012, Microbiology and immunology.

[37]  J. Chun,et al.  Elevated anti‐α‐enolase antibody levels in Kawasaki disease , 2008, Scandinavian journal of rheumatology.