BTNL2 gene polymorphisms may be associated with susceptibility to Kawasaki disease and formation of coronary artery lesions in Taiwanese children

The butyrophilin-like 2 (BTNL2) gene is a member of the B7 receptor family that probably functions as a T cell costimulatory molecule. Because altered T cell functions are implicated in dysregulation of the immune response seen in Kawasaki disease (KD), it is reasonable to speculate that BTNL2 gene is involved in the pathophysiology of KD. The purpose of this study was to investigate whether polymorphisms of the BTNL2 gene are associated with KD and the development of coronary artery lesions (CALs) in Taiwanese children. Nine-three patients with KD and 669 ethnically matched healthy controls were genotyped for BTNL2 gene rs1555115 C/G and rs2395158 A/G polymorphisms. The frequency of GG genotype of rs 1555115 was significantly higher in KD patients compared with controls (2.2% vs 0.2%, P = 0.012). The odds ratio for developing KD in individuals with rs 1555115 GG genotype was 14.7 (95% confidence interval, 2.04–105.5, P = 0.003) compared with individuals with rs 1555115 CG and CC genotypes. No significant difference was observed in the genotype and allelic frequencies of rs 2395158 polymorphism between KD patients and controls. However, the frequency of the G allele of rs 2395158 was significantly higher in KD patients with CALs than in those without CALs (P = 0.001). No significant difference was observed in the genotype and allelic frequencies of rs 1555115 polymorphism between KD patients with and without CALs. In conclusion, our results suggest that BTNL2 gene polymorphisms might be genetic markers of KD susceptibility and risk of coronary artery complication in Taiwanese children.

[1]  J. Pober,et al.  T lymphocyte-endothelial cell interactions. , 2004, Annual review of immunology.

[2]  E. Dejana,et al.  Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation1 , 2007, The Journal of Immunology.

[3]  K P Lee,et al.  Differential T cell costimulatory requirements in CD28-deficient mice. , 1993, Science.

[4]  J. Jason,et al.  Immunoregulatory changes in Kawasaki disease. , 1997, Clinical immunology and immunopathology.

[5]  D. Leung,et al.  Anti-human cardiac myosin autoantibodies in Kawasaki syndrome. , 1999, Journal of immunology.

[6]  J. Reveille,et al.  Major histocompatibility complex class II alleles in Kawasaki syndrome--lack of consistent correlation with disease or cardiac involvement. , 1992, The Journal of rheumatology.

[7]  K. Huse,et al.  Sarcoidosis is associated with a truncating splice site mutation in BTNL2 , 2005, Nature Genetics.

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

[9]  J. Newburger,et al.  ENDOTHELIAL CELL ACTIVATION AND HIGH INTERLEUKIN-1 SECRETION IN THE PATHOGENESIS OF ACUTE KAWASAKI DISEASE , 1989, The Lancet.

[10]  G. Elinder,et al.  Inflammatory parameters and soluble cell adhesion molecules in Swedish children with Kawasaki disease: relationship to cardiac lesions and intravenous immunoglobulin treatment , 1999, Acta paediatrica.

[11]  I. Matsuda,et al.  HLA antigens in mucocutaneous lymph node syndrome. , 1977, American journal of diseases of children.

[12]  G. Khuller,et al.  Evaluation of the T cells and costimulatory molecules in the protective efficacy of 30 kDa secretory protein against experimental tuberculosis , 2001, Immunology and cell biology.

[13]  A. Krensky,et al.  Epidemic and endemic HLA-B and DR associations in mucocutaneous lymph node syndrome. , 1983, Human immunology.

[14]  M. Iannuzzi,et al.  The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites. , 2005, American journal of human genetics.

[15]  Y. Danon,et al.  HLA Bw51 is increased in mucocutaneous lymph node syndrome in Israeli patients. , 2008, Tissue antigens.

[16]  Chin‐Yun Lee,et al.  Epidemiologic Features of Kawasaki Disease in Taiwan, 1996–2002 , 2004, Pediatrics.

[17]  木村 順子 Th1 and Th2 cytokine production is suppressed at the level of transcriptional regulation in Kawasaki disease , 2005 .

[18]  A. Krensky,et al.  Epedimic and endemic HLA-B and DR associations in mucocutaneous lymph node syndrome , 1983 .

[19]  B. Thiers HLA-B*5801 Allele as a Genetic Marker for Severe Cutaneous Adverse Reactions Caused by Allopurinol , 2006 .

[20]  W. Fiers,et al.  Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome , 1986, The Journal of experimental medicine.

[21]  Hirao,et al.  Circulating CD4+CD8+ T lymphocytes in patients with Kawasaki disease , 1998, Clinical and experimental immunology.

[22]  T. Kawasaki Kawasaki disease: a new disease? , 2001, Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi.

[23]  L. Rowen,et al.  BTL-II : a polymorphic locus with homology to the butyrophilin gene family, located at the border of the major histocompatibility complex class II and class III regions in human and mouse , 2000, Immunogenetics.

[24]  T. Kawasaki,et al.  HLA antigens in Kawasaki disease. , 1978, Pediatrics.

[25]  W. Klitz,et al.  The HLA class II region and susceptibility to Kawasaki disease. , 1992, Tissue antigens.

[26]  Elizabeth M. Smigielski,et al.  dbSNP: the NCBI database of genetic variation , 2001, Nucleic Acids Res..

[27]  D. Christiani,et al.  Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model. , 1996, The Journal of clinical investigation.

[28]  Yongliang Zhang,et al.  BTNL2, a Butyrophilin-Like Molecule That Functions to Inhibit T Cell Activation1 , 2006, The Journal of Immunology.

[29]  Toshiro Hara,et al.  CD25+CD4+ regulatory T cells in patients with Kawasaki disease. , 2004, The Journal of pediatrics.

[30]  N. Maclaren,et al.  Is Kawasaki HLA associated? , 1987, Progress in clinical and biological research.

[31]  R. Kaslow,et al.  Association of epidemic Kawasaki syndrome with the HLA-A2, B44, Cw5 antigen combination. , 1985, Arthritis and rheumatism.

[32]  A. Krensky,et al.  HLA antigens in mucocutaneous lymph node syndrome in New England. , 1981, Pediatrics.

[33]  G. Freeman,et al.  The B7–CD28 superfamily , 2002, Nature Reviews Immunology.

[34]  S T Sherry,et al.  Use of molecular variation in the NCBI dbSNP database , 2000, Human mutation.

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

[36]  K. Yabuta,et al.  Serum levels of tumor necrosis factor, interleukin 2 receptor, and interferon-gamma in Kawasaki disease involved coronary-artery lesions. , 1990, Clinical immunology and immunopathology.

[37]  Y. Lau,et al.  Human leucocyte antigens in Southern Chinese with Kawasaki disease , 1992, European Journal of Pediatrics.

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

[39]  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.

[40]  T. Southwood,et al.  Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins , 2002, The Lancet.