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Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children

Genes & Immunity volume 7, pages 59–64 (2006)Cite this article

Abstract

Human β-defensin (HBD)-1 is constitutively expressed in the airway, and hBD-1 plays crucial roles in innate immunity against respiratory pathogens. Asthma was associated with DEFB1 polymorphisms in Caucasians. This study investigates whether three single nucleotide polymorphisms (SNPs) in 5′-untranslated region of DEFB1 are associated with asthma phenotypes in Chinese children. Subjects aged 5–18 years were recruited from general pediatric clinics. Plasma IgE concentrations were measured by immunoassays. DEFB1 SNPs were characterized by restriction fragment length polymorphism. In all, 305 asthmatics and 156 controls were recruited. For asthma diagnosis, atopy and plasma total IgE, higher percentages of subjects with these outcomes had the minor alleles −20A and −52G (P=0.041–0.0002). For log-transformed total IgE, the covariate was positive and significant for G-20A under recessive model (P=0.001) and for G-52A under both recessive and codominant models (P=0.008 and 0.035). The recessive model covariate was also positive and significant (P=0.020) for C-44G on peripheral blood eosinophil count. The GCA haplotype of DEFB1 was significantly associated with asthma (odds ratio (95% confidence interval): 1.64 (1.05–2.57); P=0.029). These results suggest that DEFB1 is a candidate gene for asthma and atopy in children.

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References

  1. ISAAC Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998; 351: 1225–1232.

  2. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL . Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med 2000; 343: 538–543.

    Article  CAS  PubMed  Google Scholar 

  3. Illi S, von Mutius E, Lau S, Bergmann R, Niggemann B, Sommerfeld C et al. Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ 2001; 322: 390–395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Braun-Fahrländer C, Riedler J, Herz U, Eder W, Waser M, Grize L et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 2002; 347: 869–877.

    Article  PubMed  Google Scholar 

  5. Ganz T, Lehrer RI . Defensins. Pharmac Ther 1995; 66: 191–205.

    Article  CAS  Google Scholar 

  6. Ganz T . Defensins and host defense. Science 1999; 286: 420–421.

    Article  CAS  PubMed  Google Scholar 

  7. Selsted ME, Ouellette AJ . Mammalian defensins in the antimicrobial immune response. Nat Immunol 2005; 6: 551–557.

    Article  CAS  PubMed  Google Scholar 

  8. Liu L, Zhao C, Heng HH, Ganz T . The human β-defensin-1 and α-defensins are encoded by adjacent genes: two peptide families with disulfide topology share a common ancestry. Genomics 1997; 43: 316–320.

    Article  CAS  PubMed  Google Scholar 

  9. Nguyen TX, Cole AM, Lehrer RI . Evolution of primate θ-defensins: a serpentine path to a sweet tooth. Peptides 2003; 24: 1647–1654.

    Article  CAS  PubMed  Google Scholar 

  10. Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ et al. Discovery of five conserved β-defensin gene clusters using a computational search strategy. Proc Natl Acad Sci USA 2002; 99: 2129–2133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhao C, Wang I, Lehrer RI . Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 1996; 396: 319–322.

    Article  CAS  PubMed  Google Scholar 

  12. Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM . Human β-defensin-1 is a salt-sensitive antibiotic in the lung that is inactivated in cystic fibrosis. Cell 1997; 88: 553–560.

    Article  CAS  PubMed  Google Scholar 

  13. McCray Jr PB, Bentley L . Human airway epithelia express a b-defensin. Am J Respir Cell Mol Biol 1997; 16: 343–349.

    Article  CAS  PubMed  Google Scholar 

  14. Ober C, Tsalenko A, Parry R, Cox NJ . A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. Am J Hum Genet 2000; 67: 1154–1162.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hsu FC, Liang KY, Beaty TH . Multipoint linkage disequilibrium mapping approach: incorporating evidence of linkage and linkage disequilibrium from unlinked region. Genet Epidemiol 2003; 25: 1–13.

    Article  PubMed  Google Scholar 

  16. Levy H, Raby BA, Lake S, Tantisira KG, Kwiatkowski D, Lazarus R et al. Association of defensin β-1 gene polymorphisms with asthma. J Allergy Clin Immunol 2005; 115: 252–258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dörk T, Stuhrmann M . Polymorphisms of the human β-defensin-1 gene. Mol Cell Probes 1998; 12: 171–173.

    Article  PubMed  Google Scholar 

  18. Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA et al. Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci USA 1998; 95: 14961–14966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Diamond G, Bevins CL . beta-Defensins: endogenous antibiotics of the innate host defense response. Clin Immunol Immunopathol 1998; 88: 221–225.

    Article  CAS  PubMed  Google Scholar 

  20. Moser C, Weiner DJ, Lysenko E, Bals R, Weiser JN, Wilson JM . Beta-defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 2002; 70: 3068–3072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. van Wetering S, Sterk PJ, Rabe KF, Hiemstra PS . Defensins: key players or bystanders in infection, injury, and repair in the lung? J Allergy Clin Immunol 1999; 104: 1131–1138.

    Article  CAS  PubMed  Google Scholar 

  22. Panyutich AV, Hiemstra PS, van Wetering S, Ganz T . Human neutrophil defensin and serpins form complexes and inactivate each other. Am J Respir Cell Mol Biol 1995; 12: 351–357.

    Article  CAS  PubMed  Google Scholar 

  23. Matsushita I, Hasegawa K, Nakata K, Yasuda K, Tokunaga K, Keicho N . Genetic variants of human beta-defensin-1 and chronic obstructive pulmonary disease. Biochem Biophys Res Commun 2002; 291: 17–22.

    Article  CAS  PubMed  Google Scholar 

  24. Rice WG, Ganz T, Kinkade Jr JM, Selsted ME, Lehrer RI, Parmley RT . Defensin-rich dense granules of human neutrophils. Blood 1987; 70: 757–765.

    CAS  PubMed  Google Scholar 

  25. Peters SP . Heterogeneity in the pathology and treatment of asthma. Am J Med 2003; 115 (Suppl 3A): 49S–54S.

    Article  PubMed  Google Scholar 

  26. Gabrijelcic J, Acuna A, Profita M, Paterno A, Chung KF, Vignola AM et al. Neutrophil airway influx by platelet-activating factor in asthma: role of adhesion molecules and LTB4 expression. Eur Respir J 2003; 22: 290–297.

    Article  CAS  PubMed  Google Scholar 

  27. Territo MC, Ganz T, Selsted ME, Lehrer RI . Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 1989; 84: 2017–2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ et al. Identification of defensin-1, defensin-2 and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem 1996; 271: 2935–2940.

    Article  CAS  PubMed  Google Scholar 

  29. Innate Immunity in Heart, Lung, Blood Disease: Programs for Genomic Applications. IIPGA Genetic Data on DEFB1. Available at: http://innateimmunity.net/IIPGA2/PGAs/InnateImmunity/DEFB1/ and publicly accessed on 27 October 2005.

  30. Leung TF, Tang NL, Li CY, Lam CW, Wong GW, Fok TF . Association between TARC C-431T and atopy and asthma in children. J Allergy Clin Immunol 2004; 114: 199–202.

    Article  CAS  PubMed  Google Scholar 

  31. Leung TF, Liu EK, Tang NL, Ko FW, Li CY, Lam CW et al. Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children. Clin Exp Allergy 2005; 35: 1288–1294.

    Article  CAS  PubMed  Google Scholar 

  32. Leung TF, Tang NL, Chan IH, Li AM, Ha G, Lam CW . A polymorphism in the coding region of IL-13 gene is associated with atopy but not asthma in Chinese children. Clin Exp Allergy 2001; 31: 1515–1521.

    Article  CAS  PubMed  Google Scholar 

  33. American Thoracic Society. Medical section of the American Lung Association. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis 1987; 136: 225–244.

  34. Ip MS, Karlberg EM, Karlberg JP, Luk KD, Leong JC . Lung function reference values in Chinese children and adolescents in Hong Kong. I. Spirometric values and comparison with other populations. Am J Respir Crit Care Med 2000; 162: 424–429.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was financially supported by Direct Grant for Research of The Chinese University of Hong Kong.

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Authors and Affiliations

  1. Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong

    T F Leung, C Y Li, E K H Liu, E Yung & G W K Wong

  2. Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong

    N L S Tang, I H S Chan & C W K Lam

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  1. T F Leung
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Correspondence to T F Leung.

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Supplementary Information accompanies the paper on Gene website (http://www.nature.com/gene)

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Leung, T., Li, C., Liu, E. et al. Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children. Genes Immun 7, 59–64 (2006). https://doi.org/10.1038/sj.gene.6364279

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