The CCR5 (−2135C/T) Polymorphism may be Associated with the Development of Kawasaki Disease in Korean Children

BackgroundKawasaki disease (KD) is an acute vasculitis syndrome of unknown etiology that frequently affects small to medium size arteries. C-C chemokine receptor 5 (CCR5) is a chemokine receptor that binds C-C chemokines. This study investigated the association of the CCR5 (−2135C/T) polymorphism with KD in Korean children.MethodsThe study population consisted 189 Korean children with KD and 194 Korean children with congenital heart disease (CHD). CCR5 (−2135C/T) polymorphism genotypes were determined using the single-base extension method.ResultsThe allele frequencies of the CCR5 (−2135C/T) polymorphism differed significantly between CHD children and KD children (−2135T/T, 16.75% vs. 30.05%, aOR 2.14, 95% CI 1.31–3.51). The tested laboratory parameters differed significantly between the KD and CHD groups. The development of coronary artery aneurysm in KD patients was not associated with the CCR5 polymorphism.ConclusionsOur findings suggest that the T allele at the CCR5 (−2135C/T) polymorphism might be associated with the development of KD in Korean children but does not appear to be associated with the development of coronary artery aneurysm.

[1]  A. Zlotnik,et al.  Chemokines: a new classification system and their role in immunity. , 2000, Immunity.

[2]  F. Falcini.  Kawasaki disease , 2006, Current opinion in rheumatology.

[3]  Y. Kohno,et al.  Systemic Production of Vascular Endothelial Growth Factor and fms-Like Tyrosine Kinase-1 Receptor in Acute Kawasaki Disease , 2002, Circulation.

[4]  J. Clot,et al.  The strength of the chemotactic response to a CCR5 binding chemokine is determined by the level of cell surface CCR5 density , 2006, Immunology.

[5]  P. Woo,et al.  Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. , 2000, Arthritis and rheumatism.

[6]  A. Harnden,et al.  Kawasaki disease: What is the epidemiology telling us about the etiology? , 2005, International Journal of Infectious Diseases.

[7]  K Hashino,et al.  Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. , 1996, Circulation.

[8]  U. Andersson,et al.  Evaluation of the cytokine response in Kawasaki disease , 1995, The Pediatric infectious disease journal.

[9]  Jakob S. Jensen,et al.  Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. , 1999, The Journal of clinical investigation.

[10]  M. Mori,et al.  Predictors of coronary artery lesions after intravenous γ-globulin treatment in Kawasaki disease , 2000 .

[11]  Y. Ohashi,et al.  Coronary risks after high‐dose γ‐globulin in children with Kawasaki disease , 2000 .

[12]  Norishige Yoshikawa,et al.  A polymorphism in plasma platelet-activating factor acetylhydrolase is involved in resistance to immunoglobulin treatment in Kawasaki disease. , 2005, The Journal of pediatrics.

[13]  K. Yabuta,et al.  Serum levels of p60 soluble tumor necrosis factor receptor during acute Kawasaki disease. , 1994, The Journal of pediatrics.

[14]  M. Mori,et al.  Predictors of coronary artery lesions after intravenous gamma-globulin treatment in Kawasaki disease. , 2000, The Journal of pediatrics.

[15]  Jeon-Soo Shin,et al.  Tumor necrosis factor-alpha levels and promoter polymorphism in patients with Kawasaki disease in Korea. , 2003, Yonsei medical journal.

[16]  C. Mackay,et al.  The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. , 1998, The Journal of clinical investigation.

[17]  Jane C Burns,et al.  Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. , 2005, The Journal of infectious diseases.

[18]  F. Huang,et al.  Genetic variations of HLA-DRB1 and susceptibility to Kawasaki disease in Taiwanese children. , 2007, Human immunology.

[19]  G Vassart,et al.  Molecular cloning and functional expression of a new human CC-chemokine receptor gene. , 1996, Biochemistry.

[20]  H. Jäck,et al.  IgA plasma cells in vascular tissue of patients with Kawasaki syndrome. , 1997, Journal of Immunology.

[21]  B. McCrindle,et al.  Clinical Relevance of the Risk Factors for Coronary Artery Inflammation in Kawasaki Disease , 2003, Pediatric Cardiology.

[22]  I. Maruyama,et al.  Increased Serum Levels of Vascular Endothelial Growth Factor in Kawasaki Disease , 1998, Pediatric Research.

[23]  J. Burns.  Commentary: translation of Dr. Tomisaku Kawasaki's original report of fifty patients in 1967. , 2002, The Pediatric infectious disease journal.

[24]  Ogawa,et al.  Expression of Monocyte Chemoattractant Protein‐1 in Kawasaki Disease: The Anti‐Inflammatory Effect of Gamma Globulin Therapy , 2000, Scandinavian Journal of Immunology.

[25]  J. Ottenkamp,et al.  The involvement of Fc gamma receptor gene polymorphisms in Kawasaki disease , 2006, Clinical and experimental immunology.

[26]  Young Mi Hong,et al.  Insertion/Deletion Polymorphism of Angiotensin Converting Enzyme Gene in Kawasaki Disease , 2006, Journal of Korean medical science.

[27]  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.

[28]  Yusuke Nakamura,et al.  A genomewide linkage analysis of Kawasaki disease: evidence for linkage to chromosome 12 , 2006, Journal of Human Genetics.

[29]  W. Book,et al.  “Myocardial Infarction” in Adolescents: Do We Have the Correct Diagnosis? , 2005, Pediatric Cardiology.

[30]  Jong-Keuk Lee,et al.  The IL-10 (-627 A/C) Promoter Polymorphism May Be Associated With Coronary Aneurysms and Low Serum Albumin in Korean Children With Kawasaki Disease , 2007, Pediatric Research.

[31]  S Masutani,et al.  Circulating Matrix Metalloproteinases and Their Inhibitors in Patients with Kawasaki Disease , 2001, Circulation.

[32]  K. Uhlig,et al.  Predominance of mononuclear cells expressing the chemokine receptor CCR5 in synovial effusions of patients with different forms of arthritis. , 1999, Arthritis and rheumatism.

[33]  B. Chiang,et al.  Serial changes of serum interleukin-6, interleukin-8, and tumor necrosis factor alpha among patients with Kawasaki disease. , 1992, The Journal of pediatrics.

[34]  R. Rowe,et al.  Kawasaki disease: review of risk factors for coronary aneurysms. , 1986, The Journal of pediatrics.

[35]  H. Weiner,et al.  CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[36]  K. Holmes,et al.  Blinded Case‐Control Study of the Relationship between Human Coronavirus NL63 and Kawasaki Syndrome , 2006, The Journal of infectious diseases.

[37]  K. Okumura,et al.  Selective accumulation of CCR5+ T lymphocytes into inflamed joints of rheumatoid arthritis. , 1999, International immunology.

[38]  J. Newburger,et al.  A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. , 1998, The American journal of cardiology.